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KEGG pathways | MAP code | Pathways |
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MAP00260 | Glycine, serine and threonine metabolism |
UniProtKB:Accession Number | P0AB77 | Q83F40 |
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Entry name | KBL_ECOLI | Q83F40_COXBU |
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Activity | Acetyl-CoA + glycine = CoA + 2-amino-3-oxobutanoate. |
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Subunit | Homodimer. |
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Subcellular location |
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Cofactor | 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 | C00024 | C00037 | C00010 | C03508 | I00044 | I00045 | I00162 | I00161 |
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Compound | Pyridoxal phosphate | acetyl-CoA | glycine | CoA | L-2-amino-3-oxobutanoate | External aldimine intermediate (PLP-Gly) | Quinonoid intermediate (PLP-Gly) | External aldimine intermediate (PLP-2-amino-3-ketobutyric acid-CoA-tetrahedral intermediate) | External aldimine intermediate (PLP-2-amino-3-ketobutyric acid) |
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Type | aromatic ring (with nitrogen atoms),phosphate group/phosphate ion | amine group,carbohydrate,nucleotide,peptide/protein,sulfide group | amino acids | amine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl group | amino acids,carbohydrate |
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ChEBI | 18405
| 15351
| 15428 57305
| 15346
| 40673 78948
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PubChem | 1051
| 6302 444493
| 750 5257127
| 87642 6816
| 86289686 440033
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1fc4A01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Intermediate-bound:AKB-PLP |
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1fc4B01 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Intermediate-bound:AKB-PLP |
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3tqxA02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3tqxB02 |  |  |  |  |  |  |  | Bound:PLP | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1fc4A02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1fc4B02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3tqxA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3tqxB01 |  |  |  |  |  |  |  | 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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[6] | Fig.8, p.5158-5159 |
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references | [1] |
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PubMed ID | 3117785 |
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Journal | J Biol Chem |
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Year | 1987 |
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Volume | 262 |
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Pages | 14441-7 |
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Authors | Mukherjee JJ, Dekker EE |
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Title | Purification, properties, and N-terminal amino acid sequence of homogeneous Escherichia coli 2-amino-3-ketobutyrate CoA ligase, a pyridoxal phosphate-dependent enzyme. |
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[2] |
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PubMed ID | 2104756 |
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Journal | Biochim Biophys Acta |
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Year | 1990 |
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Volume | 1037 |
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Pages | 24-9 |
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Authors | Mukherjee JJ, Dekker EE |
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Title | 2-Amino-3-ketobutyrate CoA ligase of Escherichia coli: stoichiometry of pyridoxal phosphate binding and location of the pyridoxyllysine peptide in the primary structure of the enzyme. |
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[3] |
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PubMed ID | 1903922 |
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Journal | Biochem J |
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Year | 1991 |
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Volume | 275 |
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Pages | 575-9 |
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Authors | Ray S, Sarkar D, Ray M |
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Title | Aminoacetone synthase from goat liver. Involvement of arginine residue at the active site and on the stability of the enzyme. |
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[4] |
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PubMed ID | 1444446 |
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Journal | Arch Biochem Biophys |
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Year | 1992 |
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Volume | 299 |
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Pages | 147-53 |
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Authors | Mukherjee JJ, Dekker EE |
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Title | Inactivation of Escherichia coli 2-amino-3-ketobutyrate CoA ligase by phenylglyoxal and identification of an active-site arginine peptide. |
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[5] |
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PubMed ID | 7880831 |
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Journal | Biochemistry |
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Year | 1995 |
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Volume | 34 |
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Pages | 3362-7 |
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Authors | Tong H, Davis L |
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Title | 2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria: an NMR spectroscopic study of low-barrier hydrogen bonds of a pyridoxal 5'-phosphate-dependent enzyme. |
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[6] |
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Comments | X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND PYRIDOXAL PHOSPHATE, REACTION MECHANISM, SUBUNIT. |
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PubMed ID | 11318637 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 5151-60 |
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Authors | Schmidt A, Sivaraman J, Li Y, Larocque R, Barbosa JA, Smith C, Matte A, Schrag JD, Cygler M |
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Title | Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli complexed with a PLP-substrate intermediate: inferred reaction mechanism. |
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Related PDB | 1fc4 |
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Related UniProtKB | P0AB77 |
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comments | This enzyme belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family (or Type I PLP-dependent enzyme fold). This enzyme is homologous to 8-amino-7-oxononanoate synthase (EC 2.3.1.47)(D00092 in EzCatDB). According to the literature [6], this enzyme catalyzes the following reactions: (A) Formation of external aldimine (with substrate glycine) (PLP-Gly; I00044)(or transaldimination) (B) Transfer of acyl group to form an external aldimine (PLP-2-amino-3-ketobutyric acid; I00161) (C) Reformation of internal aldimine with Lys244 (of 1fc4) (or transaldimination) These reactions proceed in the following way: (A) Formation of external aldimine (with substrate glycine) (PLP-Gly; I00044)(or transaldimination): (A0) The hydrogen-bonding network, composed of His136/Ser185/Asp210, keeps the O3 atom of PLP negatively charged. (A1) The negatively charged O3 atom of PLP acts as a general base, to deprotonate the amino group of substrate, glycine. The abstracted proton is donated to NZ nitrogen of Lys244. (A2) The deprotonated amine group of glycine makes a nucleophilic attack on the C4A carbon of PLP, forming a transient geminal diamine intermediate. (A3) There must be a general base, which deprotonates the amine group of the previously glycine substrate, so that the lone pair of the amine group can attack on the C4A atom to form a double-bond, and to release the amine of the catalytic residue, Lys244. His213 may play the role as the general base. (The released Lys244 must be deprotonated, so that it can act as a general base at the next stage.) By releasing Lys244, the external aldimine intermediate (PLP-Gly; I00044) is formed. (B) Transfer of acyl group to form an external aldimine (PLP-2-amino-3-ketobutyric acid; I00161): (B1) Lys244 acts as a general base, which abstracts a proton from alpha-carbon of glycine (covalently bound to PLP; I00044), leading to the formation of a quinonoid intermediate (I00045). Here, the intermediate is stabilized by its resonance. (B2) The transferred group, acyl group of the second substrate, acetyl-CoA, is stabilized by Ser185. (B3) The activated acceptor group, the alpha-carbon (sp2; double-bonde), makes a nucleophilic attack on the thioester carbon atom of acetyl-CoA, to form a tetrahedral intermediate (I00162). The tetrahedral intermediate is stabilized by Ser185. (B4) Lys244 now acts as a general acid to protonate the sulfur atom of the leaving group, releasing the product, CoA, and forming a carbonyl group, which is stabilized by Ser185. This reaction forms an external aldimine intermediate (PLP-2-amino-3-ketobutyric acid; I00161). (C) Reformation of internal aldimine (or transaldimination): (C1) The deprotonated Lys244 acts as a nucleophile, which attacks on the C4A atom of PLP, forming a geminal diamine intermediate. (C2) There must be a general acid, to protonate the amine from the external aldimine intermediate (I00161). (His213 might play the role.) (C3) The negatively charged O3 atom of PLP abstracts a proton from the nitrogen of Lys244, and then protonates the nitrogen atom from the external aldimine intermediate, so that the lone pair of Lys244 attacks on the C4A atom again to form a double-bond, and to release the product amine group. (C4) The hydrogen-bonding network, composed of His136/Ser185/Asp210, must keep the O3 atom of PLP negatively charged during this reaction.
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created | updated |
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2012-10-26 | 2015-08-06 |
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