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CATH domain | Related DB codes (homologues) |
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3.20.20.70 : TIM Barrel | S00215,S00217,S00218,S00219,S00198,S00220,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089 |
Enzyme Name | UniProtKB | KEGG |
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| O66496 |
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Protein name | 2-dehydro-3-deoxyphosphooctonate aldolase | 3-deoxy-8-phosphooctulonate synthase2-dehydro-3-deoxy-D-octonate-8-phosphateD-arabinose-5-phosphate-lyase (pyruvate-phosphorylating)2-dehydro-3-deoxy-phosphooctonate aldolase2-keto-3-deoxy-8-phosphooctonic synthetase3-deoxy-D-manno-octulosonate-8-phosphate synthase3-deoxy-D-mannooctulosonate-8-phosphate synthetase3-deoxyoctulosonic 8-phosphate synthetaseKDOP synthasephospho-2-keto-3-deoxyoctonate aldolase |
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Synonyms | EC 2.5.1.55Phospho-2-dehydro-3-deoxyoctonate aldolase3-deoxy-D-manno-octulosonic acid 8-phosphate synthetaseKDO-8-phosphate synthetaseKDO 8-P synthaseKDOPS |
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RefSeq | NP_213056.1 (Protein) NC_000918.1 (DNA/RNA sequence)
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Pfam | PF00793 (DAHP_synth_1) [Graphical view]
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KEGG pathways | MAP code | Pathways |
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MAP00540 | Lipopolysaccharide biosynthesis |
UniProtKB:Accession Number | O66496 |
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Entry name | KDSA_AQUAE |
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Activity | Phosphoenolpyruvate + D-arabinose 5-phosphate + H(2)O = 2-dehydro-3-deoxy-D-octonate 8-phosphate + phosphate. |
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Subunit | Oligomer. |
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Subcellular location | Cytoplasm (By similarity). |
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Cofactor |
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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 | C00038 | C00074 | C01112 | C00001 | C04478 | C00009 |
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Compound | Zinc | Phosphoenolpyruvate | D-Arabinose 5-phosphate | H2O | 2-Dehydro-3-deoxy-D-octonate 8-phosphate | Orthophosphate | Transition-state with an oxocarbenium ion | A linear tetrahedral intermediate |
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Type | heavy metal | carboxyl group,phosphate group/phosphate ion | carbohydrate,phosphate group/phosphate ion | H2O | carbohydrate,carboxyl group,phosphate group/phosphate ion | phosphate group/phosphate ion |
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ChEBI | 29105
| 44897
| 16241
| 15377
| 18069
| 26078
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PubChem | 32051
| 59658623 58114173 1005
| 230 188324
| 962 22247451
| 15942880
| 22486802 1004
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1fwnA |  |  |  |  |  |  |  | Unbound | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1fwnB |  |  |  |  |  |  |  | Unbound | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1fwsA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1fwsB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1fwtA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1fwtB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Analogue:E4P | | Unbound | Unbound | Unbound | Unbound |
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1fwwA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Bound:A5P | Bound:HOH 3026 | Unbound | Unbound | Unbound | Unbound |
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1fwwB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | Bound:HOH 3060 | Unbound | Unbound | Unbound | Unbound |
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1fx6A |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1fx6B |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1fxpA |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1fxpB |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1fxqA |  |  |  |  |  |  |  | Unbound | Bound:PEP | Bound:A5P | | Unbound | Unbound | Unbound | Unbound |
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1fxqB |  |  |  |  |  |  |  | Unbound | Bound:PEP | Bound:A5P | | Unbound | Unbound | Unbound | Unbound |
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1fy6A |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Bound:A5P | | Unbound | Bound:PO4 | Unbound | Unbound |
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1fy6B |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1jcxA |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | Bound:HOH 3056 | Unbound | Unbound | Transition-state-analogue:PAI | Unbound |
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1jcxB |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | Bound:HOH 3105 | Unbound | Unbound | Transition-state-analogue:PAI | Unbound |
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1jcyA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Analogue:R5P | | Unbound | Unbound | Unbound | Unbound |
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1jcyB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1lrnA |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1lrnB |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1lroA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1lroB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1lrqA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Bound:A5P | | Unbound | Unbound | Unbound | Unbound |
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1lrqB |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1pckA |  |  |  |  |  |  |  | Analogue:_CD | Analogue:PEZ | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1pckB |  |  |  |  |  |  |  | Analogue:_CD | Analogue:PEZ | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1pcwA |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | Bound:HOH 31 | Unbound | Unbound | Transition-state-analogue:H4P | Unbound |
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1pcwB |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | Bound:HOH 93 | Unbound | Unbound | Transition-state-analogue:H4P | Unbound |
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1pe1A |  |  |  |  |  |  |  | Analogue:_CD | Analogue:2PG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1pe1B |  |  |  |  |  |  |  | Analogue:_CD | Analogue:2PG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1t8xA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Bound:A5P | | Unbound | Unbound | Unbound | Unbound |
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1t8xB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1t96A |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1t96B |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1t99A |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1t99B |  |  |  |  |  |  |  | Analogue:_CD | Unbound | Unbound | | Unbound | Bound:PO4 | Unbound | Unbound |
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1zhaA |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Analogue:R5P | | Unbound | Unbound | Unbound | Unbound |
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1zhaB |  |  |  |  |  |  |  | Analogue:_CD | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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1zjiA |  |  |  |  |  |  |  | Analogue:_CD | Analogue:2PG | Analogue:R5P | Unbound | Unbound | Unbound | Unbound | Unbound |
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1zjiB |  |  |  |  |  |  |  | Analogue:_CD | Analogue:2PG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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2a21A |  |  |  |  |  |  |  | Bound:_ZN | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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2a21B |  |  |  |  |  |  |  | Bound:_ZN | Bound:PEP | Unbound | | Unbound | Unbound | Unbound | Unbound |
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2a2iA |  |  |  |  |  |  |  | Bound:_ZN | Bound:PEP | Bound:A5P | Bound:HOH 3088 | Unbound | Unbound | Unbound | Unbound |
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2a2iB |  |  |  |  |  |  |  | Bound:_ZN | Bound:PEP | Bound:A5P | Bound:HOH 3093 | Unbound | Unbound | Unbound | Unbound |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[1] | Fig.8, p.8398-8401 |
| [2] | Scheme 1, Fig.4, p.15680-15683 |
| [3] | Fig.1, p.210-212 |
| [6] | Scheme 1, Scheme 2, p.45118-45120 |
| [7] | Scgene 1, p.7334 |
| [8] | Fig.1 |
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references | [1] |
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PubMed ID | 11115499 |
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Journal | J Biol Chem |
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Year | 2001 |
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Volume | 276 |
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Pages | 8393-402 |
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Authors | Duewel HS, Radaev S, Wang J, Woodard RW, Gatti DL |
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Title | Substrate and metal complexes of 3-deoxy-D-manno-octulosonate-8-phosphate synthase from Aquifex aeolicus at 1.9-A resolution. Implications for the condensation mechanism. |
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Related PDB | 1fwn,1fws,1fwt,1fww,1fx6,1fxp,1fxq,1fy6 |
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[2] |
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PubMed ID | 11747443 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 15676-83 |
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Authors | Wang J, Duewel HS, Woodard RW, Gatti DL |
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Title | Structures of Aquifex aeolicus KDO8P synthase in complex with R5P and PEP, and with a bisubstrate inhibitor: role of active site water in catalysis. |
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Related PDB | 1jcx,1jcy |
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[3] |
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PubMed ID | 12441100 |
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Journal | J Mol Biol |
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Year | 2002 |
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Volume | 324 |
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Pages | 205-14 |
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Authors | Wang J, Duewel HS, Stuckey JA, Woodard RW, Gatti DL |
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Title | Function of His185 in Aquifex aeolicus 3-deoxy-D-manno-octulosonate 8-phosphate synthase. |
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Related PDB | 1lrn,1lro,1lrq |
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Related UniProtKB | O66496 |
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[4] |
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PubMed ID | 14675946 |
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Journal | Drug Des Discov |
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Year | 2003 |
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Volume | 18 |
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Pages | 91-9 |
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Authors | Xu X, Wang J, Grison C, Petek S, Coutrot P, Birck MR, Woodard RW, Gatti DL |
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Title | Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase. |
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Related PDB | 1pck,1pcw,1pe1 |
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[5] |
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PubMed ID | 14701842 |
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Journal | J Biol Chem |
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Year | 2004 |
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Volume | 279 |
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Pages | 15787-94 |
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Authors | Sau AK, Li Z, Anderson KS |
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Title | Probing the role of metal ions in the catalysis of Helicobacter pylori 3-deoxy-D-manno-octulosonate-8-phosphate synthase using a transient kinetic analysis. |
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[6] |
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PubMed ID | 15308670 |
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Journal | J Biol Chem |
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Year | 2004 |
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Volume | 279 |
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Pages | 45110-20 |
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Authors | Shulami S, Furdui C, Adir N, Shoham Y, Anderson KS, Baasov T |
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Title | A reciprocal single mutation affects the metal requirement of 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthases from Aquifex pyrophilus and Escherichia coli. |
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[7] |
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PubMed ID | 15882071 |
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Journal | Biochemistry |
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Year | 2005 |
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Volume | 44 |
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Pages | 7326-35 |
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Authors | Furdui CM, Sau AK, Yaniv O, Belakhov V, Woodard RW, Baasov T, Anderson KS |
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Title | The use of (E)- and (Z)-phosphoenol-3-fluoropyruvate as mechanistic probes reveals significant differences between the active sites of KDO8P and DAHP synthases. |
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[8] |
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PubMed ID | 16156656 |
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Journal | Biochemistry |
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Year | 2005 |
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Volume | 44 |
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Pages | 12434-44 |
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Authors | Xu X, Kona F, Wang J, Lu J, Stemmler T, Gatti DL |
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Title | The catalytic and conformational cycle of Aquifex aeolicus KDO8P synthase: role of the L7 loop. |
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Related PDB | 1zha,1zji,1t8x,1t96,1t99 |
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comments | This enzyme was transferred from E.C. 4.1.2.16 to E.C. 2.5.1.55. While its counterpart enzyme from E. coli is metal-independent (class I; S00244), this enzyme, from Aquifex pyrophilus, is metal-dependent (class II). Although the catalytic residues are completely conserved, compared with those of the homologous enzymes (S00243, S00244 in EzCatDB), which are metal-dependent and metal-independent, respectively, the catalytic mechanism of this enzyme can be different from those enzymes, utilizing different catalytic residues. However, more recent studies suggested that the metal ion is not directly involved in catalysis, and that the mechanism can be similar to each other (see [6], [7]). Although the detailed mechanism has not been elucidated yet, this enzyme catalyzes the following three reactions successively (see [6], [7]). (A) Addition of the double-bonded carbon of PEP (si face) to the carbonyl group of another substrate, A5P (re face), leading to the formation of oxocarbenium ion and hydroxyl oxygen from carbonyl oxygen (see S00243): (A1) The pi-electrons on the C3=C2 double-bond of PEP make a nucleophilic attack from the si-face onto the re-face of the metal-activated aldehyde group of A5P, to form a covalent bond. (A2) Lys46 acts as a general acid, which protonates the C1-carbonyl oxygen of A5P, converting the carbonyl oxygen to hydroxyl one. (B) Addition of water to the oxocarbenium-ion intermediate, created by the condensation of PEP and A5P: (B1) Asp81 acts as a general base, activating a water molecule positioned on the re-side (opposite to si-face) of PEP. Here, His83 act as a second general base, accepting the proton of Asp81, left over by the attacking water. (B2) The activated water, the hydroxide ion, makes a nucleophilic attack on the oxocarbenium ion (C2 atom of originarily PEP), leading to the a linear intermediate. (C) Elimination of phosphate oxygen leading to formation of carbonyl group: (C1) Sidechains of Arg154, and mainchain amide of Ala102 stabilize the negative charge on the eliminated phosphate group. (C2) Lys124 acts as a general acid, which donates a proton to the eliminated phosphate group, leading to the cleavage of the C-O bond. (C3) Lys124 acts as a general base to deprotonate the hydroxyl group (created by the attacking water), leading to the formation of the carbonyl group. During these reactions, metal ions, such as zinc, assisted the reactions by orienting the substrates/intermediates.
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created | updated |
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2004-04-07 | 2009-02-26 |
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