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CATH domain | Related DB codes (homologues) |
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3.40.640.10 : Aspartate Aminotransferase; domain 2 | D00092,D00101,D00102,D00103,D00104,D00107,D00108,D00109,D00255,D00257,D00258,D00265,D00269,D00515,M00031,D00279 | 3.90.1150.10 : Aspartate Aminotransferase, domain 1 | D00092,D00101,D00102,D00103,D00104,D00107,D00108,D00109,D00255,D00257,D00258,D00265,D00269,D00515,M00031,D00279 |
KEGG pathways | MAP code | Pathways |
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MAP00260 | Glycine, serine and threonine metabolism | MAP00460 | Cyanoamino acid metabolism | MAP00670 | One carbon pool by folate | MAP00680 | Methane metabolism |
UniProtKB:Accession Number | P0A825 | Q5SI56 | Q7SIB6 | P50431 | P07511 | P34896 | P34897 |
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Entry name | GLYA_ECOLI | GLYA_THET8 | Q7SIB6_BACST | GLYC_MOUSE | GLYC_RABIT | GLYC_HUMAN | GLYM_HUMAN |
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Activity | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. | 5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine. |
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Subunit | Homotetramer. | Homotetramer (By similarity). |
| Homotetramer. | Homotetramer. | Homotetramer. | Homotetramer. |
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Subcellular location | Cytoplasm. | Cytoplasm (By similarity). |
| Cytoplasm. | Cytoplasm. | Cytoplasm. | Mitochondrion. |
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Cofactor | Pyridoxal phosphate. | Pyridoxal phosphate (By similarity). | Pyridoxal phosphate.,Pyridoxal phosphate (By similarity). | Pyridoxal phosphate (By similarity). | Pyridoxal phosphate. | Pyridoxal phosphate. | Pyridoxal phosphate. |
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Compound table: links to PDB-related databases & PoSSuM |
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| Cofactors | Substrates | Products | intermediates |
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KEGG-id | C00018 | C00065 | C00101 | C00037 | C00143 | C00001 | I00043 | C00067 | I00045 | I00046 | I00047 | I00044 | I00048 |
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Compound | Pyridoxal phosphate | L-Serine | Tetrahydrofolate | Glycine | 5,10-Methylenetetrahydrofolate | H2O | External aldimine intermediate (PLP-L-Ser) | Formaldehyde | Quinonoid intermediate (PLP-Gly) | 5-hydroxymethylene-tetrahydrofolate | 5-iminium-tetrahydrofolate | External aldimine intermediate (PLP-Gly) | Gem-diamine transition-state (active-site-Lys-PLP-Gly) |
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Type | aromatic ring (with nitrogen atoms),phosphate group/phosphate ion | amino acids,carbohydrate | amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group | amino acids | amino acids,amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group | H2O |
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ChEBI | 18405
| 17115 33384
| 15635 20506
| 15428 57305
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| 15377
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PubChem | 1051
| 5951 6857581
| 5460413 91443
| 5257127 750
| 439175
| 22247451 962
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| | | | | | | | | | | | | | | | | | | | |
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1dfoA01 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:PLG | Unbound |
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1dfoB01 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:PLG | Unbound |
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1dfoC01 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:PLG | Unbound |
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1dfoD01 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:PLG | Unbound |
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1eqbA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:GLY-PLP | Unbound |
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1eqbB01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:GLY-PLP | Unbound |
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1eqbC01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:GLY-PLP | Unbound |
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1eqbD01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FFO | | Intermediate-bound:GLY-PLP | Unbound |
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2dkjA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2dkjB01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kkjA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kkpA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Intermediate-bound:SER-PLP | | Unbound | Unbound | | Unbound | Unbound |
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1kl1A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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1kl2A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FON | | Intermediate-bound:GLY-PLP | Unbound |
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1kl2B02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:FON | | Intermediate-bound:GLY-PLP | Unbound |
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1yjsA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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1yjyA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Intermediate-bound:SER-PLP | | Unbound | Unbound | | Unbound | Unbound |
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1yjzA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vgtA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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2vguA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Intermediate-bound:SER-PLP | | Unbound | Unbound | | Unbound | Unbound |
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2vgvA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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2vgwA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:GLY-PLP-LYS 226 |
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2vi9A01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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2viaA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Intermediate-bound:SER-PLP | | Unbound | Unbound | | Unbound | Unbound |
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2vibA01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Intermediate-bound:GLY-PLP | Unbound |
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1ejiA02 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Intermediate-bound:PLG | Intermediate-bound:THF | | Unbound | Unbound |
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1ejiB02 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Intermediate-bound:PLG | Intermediate-bound:THF | | Unbound | Unbound |
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1ejiC02 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:PLG-LYS 257 |
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1ejiD02 |  |  |  |  |  |  |  | Analogue:PLG | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-bound:THF | | Unbound | Transition-state-bound:PLG-LYS 257 |
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1cj0A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1cj0B02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ls3A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:GLY-PLP-LYS 229 |
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1ls3B02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:TGF | | Unbound | Unbound |
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1ls3C02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:GLY-PLP-LYS 229 |
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1ls3D02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Intermediate-analogue:TGF | | Unbound | Unbound |
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1rv3A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv3B02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:GLY-PLP-LYS 257 |
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1rv4A02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv4B02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvuA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvuB02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvyA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Transition-state-bound:PLG-LYS 257 |
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1rvyB02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1bj4A01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2a7vA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1dfoA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1dfoB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1dfoC02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1dfoD02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1eqbA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1eqbB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1eqbC02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1eqbD02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2dkjA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2dkjB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kkjA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kkpA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kl1A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kl2A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1kl2B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1yjsA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1yjyA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1yjzA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vgtA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vguA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vgvA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vgwA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vi9A02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2viaA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2vibA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ejiA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ejiB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ejiC01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ejiD01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1cj0A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1cj0B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ls3A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ls3B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ls3C01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1ls3D01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv3A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv3B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv4A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rv4B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvuA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvuB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvyA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1rvyB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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1bj4A02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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2a7vA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | | Unbound | | Unbound | Unbound | | Unbound | Unbound |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[17] | Fig.6, p.24360-24361 |
| [22] | Figure 1, p.1105, p.1110-1113 |
| [25] | Scheme 1, p.8352-8357 |
| [26] | Fig.17, Fig.18, p.394-397 |
| [28] | Scheme 1, p.7499 |
| [29] | Fig.1, p.13320-13223 |
| [30] | Scheme 1, p.5974-5975 |
| [31] | Fig.4, p.1443-1446 |
| [33] | p.411-413 |
| [34] | Scheme 1, p.156-157, p.162-166 |
| [36] | Scheme 1 |
| [38] | Scheme I, Scheme II, p.17168 |
| [41] | Fig.1, p.24-25, p.27-28 |
| [47] | Fig.1, p.6865-6867 |
| [49] | Scheme 1, p.6930, p.6935-6936 |
| [50] | p.4154-4155 |
|
references | [1] |
---|
PubMed ID | 3536510 |
---|
Journal | Eur J Biochem |
---|
Year | 1986 |
---|
Volume | 161 |
---|
Pages | 45-9 |
---|
Authors | Schirch V, Schirch D, Martini F, Bossa F |
---|
Title | Serine hydroxymethyltransferase. Effect of proteases on the activity and structure of the cytosolic enzyme. |
---|
[2] |
---|
PubMed ID | 1849406 |
---|
Journal | Biochem J |
---|
Year | 1991 |
---|
Volume | 274 |
---|
Pages | 807-12 |
---|
Authors | Malthouse JP, Milne JJ, Gariani LS |
---|
Title | A comparative study of the kinetics and stereochemistry of the serine hydroxymethyltransferase- and tryptophan synthase-catalysed exchange of the pro-2R and pro-2S protons of glycine. |
---|
[3] |
---|
PubMed ID | 1765122 |
---|
Journal | Experientia |
---|
Year | 1991 |
---|
Volume | 47 |
---|
Pages | 1104-18 |
---|
Authors | Smith DM, Thomas NR, Gani D |
---|
Title | A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level. |
---|
[4] |
---|
PubMed ID | 1536856 |
---|
Journal | Biochemistry |
---|
Year | 1992 |
---|
Volume | 31 |
---|
Pages | 2155-64 |
---|
Authors | Stover P, Schirch V |
---|
Title | Enzymatic mechanism for the hydrolysis of 5,10-methenyltetrahydropteroylglutamate to 5-formyltetrahydropteroylglutamate by serine hydroxymethyltransferase. |
---|
[5] |
---|
PubMed ID | 1577761 |
---|
Journal | J Biol Chem |
---|
Year | 1992 |
---|
Volume | 267 |
---|
Pages | 9289-93 |
---|
Authors | Usha R, Savithri HS, Rao NA |
---|
Title | Arginine residues involved in binding of tetrahydrofolate to sheep liver serine hydroxymethyltransferase. |
---|
[6] |
---|
PubMed ID | 8405393 |
---|
Journal | FEBS Lett |
---|
Year | 1993 |
---|
Volume | 331 |
---|
Pages | 145-9 |
---|
Authors | Pascarella S, Schirch V, Bossa F |
---|
Title | Similarity between serine hydroxymethyltransferase and other pyridoxal phosphate-dependent enzymes. |
---|
[7] |
---|
PubMed ID | 8226831 |
---|
Journal | J Biol Chem |
---|
Year | 1993 |
---|
Volume | 268 |
---|
Pages | 23132-8 |
---|
Authors | Schirch D, Delle Fratte S, Iurescia S, Angelaccio S, Contestabile R, Bossa F, Schirch V |
---|
Title | Function of the active-site lysine in Escherichia coli serine hydroxymethyltransferase. |
---|
[8] |
---|
PubMed ID | 8478924 |
---|
Journal | J Mol Biol |
---|
Year | 1993 |
---|
Volume | 230 |
---|
Pages | 1094-6 |
---|
Authors | Stover P, Kruschwitz H, Schirch V, Wright HT |
---|
Title | Diffraction grade crystals of Escherichia coli serine hydroxymethyltransferase. |
---|
[9] |
---|
PubMed ID | 7947980 |
---|
Journal | Biochim Biophys Acta |
---|
Year | 1994 |
---|
Volume | 1209 |
---|
Pages | 40-50 |
---|
Authors | Bhaskar B, Prakash V, Savithri HS, Rao NA |
---|
Title | Interactions of L-serine at the active site of serine hydroxymethyltransferases: induction of thermal stability. |
---|
[10] |
---|
PubMed ID | 8003988 |
---|
Journal | Protein Sci |
---|
Year | 1994 |
---|
Volume | 3 |
---|
Pages | 701-5 |
---|
Authors | Pascarella S, Bossa F |
---|
Title | Similarity between pyridoxal/pyridoxamine phosphate-dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes. |
---|
[11] |
---|
PubMed ID | 8674620 |
---|
Journal | Biochem Soc Trans |
---|
Year | 1996 |
---|
Volume | 24 |
---|
Pages | 132S |
---|
Authors | Fitzpatrick TB, Malthouse JP |
---|
Title | Proof that serine hydroxymethyltransferase retains its specificity for the pro-2S proton of glycine in the absence of tetrahydrofolate. |
---|
[12] |
---|
PubMed ID | 8910307 |
---|
Journal | J Biol Chem |
---|
Year | 1996 |
---|
Volume | 271 |
---|
Pages | 27311-20 |
---|
Authors | Cai K, Schirch V |
---|
Title | Structural studies on folding intermediates of serine hydroxymethyltransferase using fluorescence resonance energy transfer. |
---|
[13] |
---|
PubMed ID | 8621691 |
---|
Journal | J Biol Chem |
---|
Year | 1996 |
---|
Volume | 271 |
---|
Pages | 2987-94 |
---|
Authors | Cai K, Schirch V |
---|
Title | Structural studies on folding intermediates of serine hydroxymethyltransferase using single tryptophan mutants. |
---|
[14] |
---|
PubMed ID | 8860659 |
---|
Journal | Protein Expr Purif |
---|
Year | 1996 |
---|
Volume | 7 |
---|
Pages | 323-8 |
---|
Authors | Iurescia S, Condo I, Angelaccio S, Delle Fratte S, Bossa F |
---|
Title | Site-directed mutagenesis techniques in the study of Escherichia coli serine hydroxymethyltransferase. |
---|
[15] |
---|
PubMed ID | 9584848 |
---|
Journal | Acta Biochim Pol |
---|
Year | 1997 |
---|
Volume | 44 |
---|
Pages | 679-88 |
---|
Authors | Talwar R, Jagath JR, Datta A, Prakash V, Savithri HS, Rao NA |
---|
Title | The role of lysine-256 in the structure and function of sheep liver recombinant serine hydroxymethyltransferase. |
---|
[16] |
---|
PubMed ID | 9398220 |
---|
Journal | Biochemistry |
---|
Year | 1997 |
---|
Volume | 36 |
---|
Pages | 14956-64 |
---|
Authors | Kastanos EK, Woldman YY, Appling DR |
---|
Title | Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes in de novo purine synthesis in Saccharomyces cerevisiae. |
---|
[17] |
---|
PubMed ID | 9305893 |
---|
Journal | J Biol Chem |
---|
Year | 1997 |
---|
Volume | 272 |
---|
Pages | 24355-62 |
---|
Authors | Jagath JR, Sharma B, Rao NA, Savithri HS |
---|
Title | The role of His-134, -147, and -150 residues in subunit assembly, cofactor binding, and catalysis of sheep liver cytosolic serine hydroxymethyltransferase. |
---|
[18] |
---|
Comments | X-ray crystallography |
---|
PubMed ID | 9757129 |
---|
Journal | Acta Crystallogr D Biol Crystallogr |
---|
Year | 1998 |
---|
Volume | 54 |
---|
Pages | 1030-1 |
---|
Authors | Renwick SB, Skelly JV, Chave KJ, Sanders PG, Snell K, Baumann U |
---|
Title | Purification, crystallization and preliminary X-ray analysis of human recombinant cytosolic serine hydroxymethyltransferase. |
---|
Related PDB | 1bj4 |
---|
[19] |
---|
PubMed ID | 9523719 |
---|
Journal | Eur J Biochem |
---|
Year | 1998 |
---|
Volume | 252 |
---|
Pages | 113-7 |
---|
Authors | Fitzpatrick TB, Malthouse JP |
---|
Title | A substrate-induced change in the stereospecificity of the serine-hydroxymethyltransferase-catalysed exchange of the alpha-protons of amino acids--evidence for a second catalytic site. |
---|
[20] |
---|
PubMed ID | 9843671 |
---|
Journal | J Struct Biol |
---|
Year | 1998 |
---|
Volume | 123 |
---|
Pages | 169-74 |
---|
Authors | Kazanina G, Radaev S, Wright HT, Schirch V |
---|
Title | Crystal forms and subunit stoichiometry of serine hydroxymethyltransferase. |
---|
[21] |
---|
PubMed ID | 9761478 |
---|
Journal | Protein Sci |
---|
Year | 1998 |
---|
Volume | 7 |
---|
Pages | 1976-82 |
---|
Authors | Pascarella S, Angelaccio S, Contestabile R, Delle Fratte S, Di Salvo M, Bossa F |
---|
Title | The structure of serine hydroxymethyltransferase as modeled by homology and validated by site-directed mutagenesis. |
---|
[22] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 11-480 |
---|
Medline ID | 98428667 |
---|
PubMed ID | 9753690 |
---|
Journal | Structure |
---|
Year | 1998 |
---|
Volume | 6 |
---|
Pages | 1105-16 |
---|
Authors | Renwick SB, Snell K, Baumann U |
---|
Title | The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy. |
---|
Related UniProtKB | P34896 |
---|
[23] |
---|
PubMed ID | 10600164 |
---|
Journal | Arch Biochem Biophys |
---|
Year | 1999 |
---|
Volume | 372 |
---|
Pages | 271-9 |
---|
Authors | di Salvo ML, Delle Fratte S, Maras B, Bossa F, Wright HT, Schirch V |
---|
Title | Deamidation of asparagine residues in a recombinant serine hydroxymethyltransferase. |
---|
[24] |
---|
PubMed ID | 10493937 |
---|
Journal | Biochem J |
---|
Year | 1999 |
---|
Volume | 343 Pt 1 |
---|
Pages | 257-63 |
---|
Authors | Krishna Rao JV, Jagath JR, Sharma B, Appaji Rao N, Savithri HS |
---|
Title | Asp-89: a critical residue in maintaining the oligomeric structure of sheep liver cytosolic serine hydroxymethyltransferase. |
---|
[25] |
---|
PubMed ID | 10387080 |
---|
Journal | Biochemistry |
---|
Year | 1999 |
---|
Volume | 38 |
---|
Pages | 8347-58 |
---|
Authors | Scarsdale JN, Kazanina G, Radaev S, Schirch V, Wright HT |
---|
Title | Crystal structure of rabbit cytosolic serine hydroxymethyltransferase at 2.8 A resolution: mechanistic implications. |
---|
Related PDB | 1cj0 |
---|
[26] |
---|
PubMed ID | 10828359 |
---|
Journal | Adv Enzyme Regul |
---|
Year | 2000 |
---|
Volume | 40 |
---|
Pages | 353-403 |
---|
Authors | Snell K, Baumann U, Byrne PC, Chave KJ, Renwick SB, Sanders PG, Whitehouse SK |
---|
Title | The genetic organization and protein crystallographic structure of human serine hydroxymethyltransferase. |
---|
[27] |
---|
PubMed ID | 10970801 |
---|
Journal | Biochem J |
---|
Year | 2000 |
---|
Volume | 350 Pt 3 |
---|
Pages | 849-53 |
---|
Authors | Talwar R, Leelavathy V, Krishna Rao JV, Appaji Rao N, Savithri HS |
---|
Title | Role of pro-297 in the catalytic mechanism of sheep liver serine hydroxymethyltransferase. |
---|
[28] |
---|
Comments | X-ray crystallography |
---|
PubMed ID | 10858298 |
---|
Journal | Biochemistry |
---|
Year | 2000 |
---|
Volume | 39 |
---|
Pages | 7492-500 |
---|
Authors | Contestabile R, Angelaccio S, Bossa F, Wright HT, Scarsdale N, Kazanina G, Schirch V |
---|
Title | Role of tyrosine 65 in the mechanism of serine hydroxymethyltransferase. |
---|
Related PDB | 1eqb |
---|
[29] |
---|
Comments | X-ray crystallography |
---|
PubMed ID | 11063567 |
---|
Journal | Biochemistry |
---|
Year | 2000 |
---|
Volume | 39 |
---|
Pages | 13313-23 |
---|
Authors | Szebenyi DM, Liu X, Kriksunov IA, Stover PJ, Thiel DJ |
---|
Title | Structure of a murine cytoplasmic serine hydroxymethyltransferase quinonoid ternary complex: evidence for asymmetric obligate dimers. |
---|
Related PDB | 1eji |
---|
[30] |
---|
PubMed ID | 10998057 |
---|
Journal | Eur J Biochem |
---|
Year | 2000 |
---|
Volume | 267 |
---|
Pages | 5967-76 |
---|
Authors | Rao JV, Prakash V, Rao NA, Savithri HS |
---|
Title | The role of Glu74 and Tyr82 in the reaction catalyzed by sheep liver cytosolic serine hydroxymethyltransferase. |
---|
[31] |
---|
PubMed ID | 10691982 |
---|
Journal | Eur J Biochem |
---|
Year | 2000 |
---|
Volume | 267 |
---|
Pages | 1441-6 |
---|
Authors | Talwar R, Jagath JR, Rao NA, Savithri HS |
---|
Title | His230 of serine hydroxymethyltransferase facilitates the proton abstraction step in catalysis. |
---|
[32] |
---|
PubMed ID | 10716626 |
---|
Journal | Int J Biochem Cell Biol |
---|
Year | 2000 |
---|
Volume | 32 |
---|
Pages | 289-301 |
---|
Authors | Ogawa H, Gomi T, Fujioka M |
---|
Title | Serine hydroxymethyltransferase and threonine aldolase: are they identical? |
---|
[33] |
---|
PubMed ID | 10762066 |
---|
Journal | Int J Biochem Cell Biol |
---|
Year | 2000 |
---|
Volume | 32 |
---|
Pages | 405-16 |
---|
Authors | Rao NA, Talwar R, Savithri HS |
---|
Title | Molecular organization, catalytic mechanism and function of serine hydroxymethyltransferase--a potential target for cancer chemotherapy. |
---|
[34] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) |
---|
Medline ID | 20124005 |
---|
PubMed ID | 10656824 |
---|
Journal | J Mol Biol |
---|
Year | 2000 |
---|
Volume | 296 |
---|
Pages | 155-68 |
---|
Authors | Scarsdale JN, Radaev S, Kazanina G, Schirch V, Wright HT |
---|
Title | Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate. |
---|
Related PDB | 1dfo |
---|
Related UniProtKB | P0A825 |
---|
[35] |
---|
PubMed ID | 11305908 |
---|
Journal | Biochemistry |
---|
Year | 2001 |
---|
Volume | 40 |
---|
Pages | 4932-9 |
---|
Authors | Liu X, Szebenyi DM, Anguera MC, Thiel DJ, Stover PJ |
---|
Title | Lack of catalytic activity of a murine mRNA cytoplasmic serine hydroxymethyltransferase splice variant: evidence against alternative splicing as a regulatory mechanism. |
---|
[36] |
---|
PubMed ID | 11737206 |
---|
Journal | Eur J Biochem |
---|
Year | 2001 |
---|
Volume | 268 |
---|
Pages | 6508-25 |
---|
Authors | Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D'Aguanno S, Bossa F |
---|
Title | l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions. |
---|
[37] |
---|
PubMed ID | 12356312 |
---|
Journal | Biochemistry |
---|
Year | 2002 |
---|
Volume | 41 |
---|
Pages | 12115-23 |
---|
Authors | Bhatt AN, Prakash K, Subramanya HS, Bhakuni V |
---|
Title | Different unfolding pathways for mesophilic and thermophilic homologues of serine hydroxymethyltransferase. |
---|
[38] |
---|
PubMed ID | 11877399 |
---|
Journal | J Biol Chem |
---|
Year | 2002 |
---|
Volume | 277 |
---|
Pages | 17161-9 |
---|
Authors | Trivedi V, Gupta A, Jala VR, Saravanan P, Rao GS, Rao NA, Savithri HS, Subramanya HS |
---|
Title | Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism. |
---|
Related PDB | 1kkj,1kkp,1kl1,1kl2 |
---|
[39] |
---|
PubMed ID | 12089472 |
---|
Journal | J Biosci |
---|
Year | 2002 |
---|
Volume | 27 |
---|
Pages | 233-42 |
---|
Authors | Jala VR, Prakash V, Rao NA, Savithri HS |
---|
Title | Overexpression and characterization of dimeric and tetrameric forms of recombinant serine hydroxymethyltransferase from Bacillus stearothermophilus. |
---|
[40] |
---|
PubMed ID | 12392447 |
---|
Journal | Biochem J |
---|
Year | 2003 |
---|
Volume | 369 |
---|
Pages | 469-76 |
---|
Authors | Jala VR, Appaji Rao N, Savithri HS |
---|
Title | Identification of amino acid residues, essential for maintaining the tetrameric structure of sheep liver cytosolic serine hydroxymethyltransferase, by targeted mutagenesis. |
---|
[41] |
---|
PubMed ID | 12686103 |
---|
Journal | Biochim Biophys Acta |
---|
Year | 2003 |
---|
Volume | 1647 |
---|
Pages | 24-9 |
---|
Authors | Appaji Rao N, Ambili M, Jala VR, Subramanya HS, Savithri HS |
---|
Title | Structure-function relationship in serine hydroxymethyltransferase. |
---|
[42] |
---|
PubMed ID | 12686123 |
---|
Journal | Biochim Biophys Acta |
---|
Year | 2003 |
---|
Volume | 1647 |
---|
Pages | 138-42 |
---|
Authors | Malthouse JP |
---|
Title | Stereospecificity of alpha-proton exchange reactions catalysed by pyridoxal-5'-phosphate-dependent enzymes. |
---|
[43] |
---|
PubMed ID | 12902326 |
---|
Journal | J Biol Chem |
---|
Year | 2003 |
---|
Volume | 278 |
---|
Pages | 41789-97 |
---|
Authors | Angelaccio S, Chiaraluce R, Consalvi V, Buchenau B, Giangiacomo L, Bossa F, Contestabile R |
---|
Title | Catalytic and thermodynamic properties of tetrahydromethanopterin-dependent serine hydroxymethyltransferase from Methanococcus jannaschii. |
---|
[44] |
---|
PubMed ID | 12773539 |
---|
Journal | J Biol Chem |
---|
Year | 2003 |
---|
Volume | 278 |
---|
Pages | 31088-94 |
---|
Authors | Fu TF, Boja ES, Safo MK, Schirch V |
---|
Title | Role of proline residues in the folding of serine hydroxymethyltransferase. |
---|
[45] |
---|
PubMed ID | 12514178 |
---|
Journal | J Biol Chem |
---|
Year | 2003 |
---|
Volume | 278 |
---|
Pages | 10142-9 |
---|
Authors | Zanetti KA, Stover PJ |
---|
Title | Pyridoxal phosphate inhibits dynamic subunit interchange among serine hydroxymethyltransferase tetramers. |
---|
[46] |
---|
PubMed ID | 12438316 |
---|
Journal | J Biol Chem |
---|
Year | 2003 |
---|
Volume | 278 |
---|
Pages | 2645-53 |
---|
Authors | Fu TF, Scarsdale JN, Kazanina G, Schirch V, Wright HT |
---|
Title | Location of the pteroylpolyglutamate-binding site on rabbit cytosolic serine hydroxymethyltransferase. |
---|
Related PDB | 1ls3 |
---|
[47] |
---|
PubMed ID | 15170323 |
---|
Journal | Biochemistry |
---|
Year | 2004 |
---|
Volume | 43 |
---|
Pages | 6865-76 |
---|
Authors | Szebenyi DM, Musayev FN, di Salvo ML, Safo MK, Schirch V |
---|
Title | Serine hydroxymethyltransferase: role of glu75 and evidence that serine is cleaved by a retroaldol mechanism. |
---|
Related PDB | 1rv3,1rv4,1rvu,1rvy |
---|
[48] |
---|
PubMed ID | 15273312 |
---|
Journal | Protein Sci |
---|
Year | 2004 |
---|
Volume | 13 |
---|
Pages | 2184-95 |
---|
Authors | Bhatt AN, Khan MY, Bhakuni V |
---|
Title | The C-terminal domain of dimeric serine hydroxymethyltransferase plays a key role in stabilization of the quaternary structure and cooperative unfolding of protein: domain swapping studies with enzymes having high sequence identity. |
---|
[49] |
---|
PubMed ID | 15865438 |
---|
Journal | Biochemistry |
---|
Year | 2005 |
---|
Volume | 44 |
---|
Pages | 6929-37 |
---|
Authors | Bhavani S, Trivedi V, Jala VR, Subramanya HS, Kaul P, Prakash V, Appaji Rao N, Savithri HS |
---|
Title | Role of Lys-226 in the catalytic mechanism of Bacillus stearothermophilus serine hydroxymethyltransferase--crystal structure and kinetic studies. |
---|
Related PDB | 1yjs,1yjy,1yjz |
---|
[50] |
---|
PubMed ID | 17651438 |
---|
Journal | FEBS J |
---|
Year | 2007 |
---|
Volume | 274 |
---|
Pages | 4148-60 |
---|
Authors | Rajaram V, Bhavani BS, Kaul P, Prakash V, Appaji Rao N, Savithri HS, Murthy MR |
---|
Title | Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory. |
---|
Related PDB | 2vgt,2vgu,2vgv,2vgw |
---|
comments | This enzyme belongs to the type-I PLP-dependent enzyme superfamily (Aspartate aminotransferase superfamily, AAT; D00101 in EzCatDB). There have been several possible catalytic mechanisms proposed for this enzyme (see [47]). Among these mechanisms, including the retro-aldol cleavage reaction (see [34], [38]) and the nucleophilic direct displacement reaction (see [38]), the concerted mechanism that combines the retro-aldol cleavage and the nucleophilic direct displacement reaction seems most likely (see [47], [50]). This catalytic mechanism is composed of the following reactions: (A) Formation of external aldimine (with amine group of L-Serine): Exchange of double-bonded atoms. (B) SN1-like transfer of hydroxymethyl group from Ser-PLP to N5 of tetrahydrofolate (THF), forming a quinonoid intermediate of PLP-Gly (I00045) and a carbinolamine intermediate of THF (I00046). (C) Elimination of hydroxyl group from the carbinolamine intermediate, forming an iminium cation intermediate of THF (I00047). (D) Intramolecular addition of N10 to the carbon atom of the iminium cation. (E or D') Isomerization (change in the position of double-bond), forming an external aldimine (Gly-PLP) from the quinonoid intermediate. (F) Formation of internal aldimine, leading to the elimination of the product (Gly) from PLP: Exchange of double-bonded atoms. These reactions proceed as follows: (A) Formation of external aldimine (with amine group of L-Serine): Exchange of double-bonded atoms. (A1) The negatively charged O3 atom of PLP modulates the pKa of the alpha-amino group of substrate, L-serine (Ser), and also the pKa of the internal aldimine with Lys229 (of 1dfo). Here, according to the literature from D00101 (D00101 [46], [59] & [61]), the imine-pyridine torsion (or strain) of PLP-Schiff base lowers pKa of the internal aldimine, without lowering pKa of the external aldimine. In any case, the difference in the pKa values facilitates the proton transfer from the alpha-amino group of Ser to the NZ nitrogen of Lys229. Moreover, the alpha-carboxylate of Ser may deprotonate the nucleophile, the alpha-amino group of Ser (see D00106 [10]). (A2) The deprotonated amine group of Ser makes a nucleophilic attack on the C4' carbon of PLP, forming a transient geminal diamine intermediate. (A3) There must be a general base, which deprotonates the amine group of the previously Ser substrate, so that the lone pair of the amine group can attack on the C4' atom to form a double-bond, and to release the amine of the catalytic residue, Lys229. Considering the active-site structure, Tyr55' (from the adjacent chain) may play the role as the general base, although the literature has not mentioned it (except for the literature from D00101 [11]). (The released Lys229 must be deprotonated, so that it can act as a general base at the final stage.) However, according to the active site structure of geminal diamine intermediate, the short distance between the NZ atom of Lys229 and amine group of the amino acid substrate suggests that a direct proton transfer can occur. Moreover, according to the literature [34], Thr226 stabilizes the unprotonated NZ atom of Lys229 (acting as a modulator). (A4) The lone pair of the amine group (of Ser) makes a nucleophilic attack on the C4' atom to form a double-bond, releasing the amine of Lys229, leading to the formation of the external aldimine with L-Ser. (B) Transfer of hydroxymethyl group from Ser-PLP to N5 of tetrahydrofolate (THF), forming a quinonoid intermediate of PLP-Gly (I00045) and a carbinolamine intermediate of THF (I00046). (B1) Asp200 interacts with the N1 atom of PLP, modulating and enhancing the activity of the PLP cofactor as an electron sink, leading to polarization of the C2-C3 (or alpha-beta carbon atoms) bond, with positive charge accumulating on the C3 atom (see [47]; D00101 [17], [24]). The hydrogen-bond from Glu57 to O-gamma increases the charge on the C3 even further (Glu57 acting as a modulator?). Thus, the polarized C2-C3 bond is easily broken (see [47]). (B2) A general base deprotonates the N5 atom of THF for its activation. (A water can be the weak base.) (B3) The activated N5 atom makes a nucleophilic attack on the beta-carbon (or C3) atom of Ser-PLP, cleaving the C2-C3 bond to give a carbinolamine intermediate (I00046; THF-CH2OH) and a quinonoid intermediate of Gly-PLP (I00045). Asp200 may stabilize the quinonoid intermediate, through the interaction with the N1 atom of PLP (see D00271 [8]). This transfer reaction is an SN2-like reaction (see [47]). (C) Elimination of hydroxyl group from the carbinolamine intermediate, forming an iminium cation intermediate of THF (I00047). (C1) Glu57 acts as a general acid to protonate the hydroxyl group of the carbinolamine intermediate. (C2) The hydroxyl group is eliminated from the intermediate to form a water molecule, forming a 5-iminium-THF (I00047). (D) Intramolecular addition of N10 to the carbon atom of the iminium cation. (D1) Glu57 acts as a general base to deprotonate the N10 atom (added group) of the iminium cation intermediate. (D2) The activated the N10 atom makes a nucleophilic attack on the carbon atom of the iminium cation (addition site), forming a covalent bond with it. (E or D') Isomerization (change in the position of double-bond), forming an external aldimine (Gly-PLP) from the quinonoid intermediate. (E1) Although Tyr65' stabilizes the quinonoid intermediate (see [30]), it may act as a general acid to protonate the C2 atom of the quinonoid intermediate. (E2) This reaction produces an external aldimine intermediate (I00044; Gly-PLP). (F) Formation of internal aldimine, leading to the elimination of the product (Gly) from PLP: Exchange of double-bonded atoms. (F1) Thr226 stabilizes the unprotonated NZ atom of Lys229 (acting as a modulator). (F2) The deprotonated amine group of Lys229 makes a nucleophilic attack on the C4' carbon of the PLP of the external aldimine, forming a transient geminal diamine intermediate. (F3) The lone pair of the amine nitrogen of Lys229 can attack on the C4' atom to form a double-bond, and to release the amine of the second product, Gly. (F4) The negatively charged O3 atom of PLP modulates the pKa of the alpha-amino group of product, Gly, and also the pKa of the internal aldimine with Lys229. In any case, the difference in the pKa values facilitates the proton transfer from the NZ nitrogen of Lys229 to the alpha-amine group of Gly. The alpha-carboxylate of Gly may protonate the leaving group, the alpha-amino group of Gly (see D00106 [10]).
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created | updated |
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2004-11-25 | 2009-02-26 |
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