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CATH domain | Related DB codes (homologues) |
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3.40.50.720 : Rossmann fold | S00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00274,D00275,M00035,T00109 | 3.90.25.10 : UDP-galactose 4-epimerase; domain 1 | D00513,D00601,D00604,D00274,D00275 |
KEGG pathways | MAP code | Pathways |
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MAP00520 | Nucleotide sugars metabolism | MAP00521 | Streptomycin biosynthesis | MAP00523 | Polyketide sugar unit biosynthesis | MAP01055 | Biosynthesis of vancomycin group antibiotics |
UniProtKB:Accession Number | P27830 | Q9EU31 | P26391 | P95780 | Q8GIP9 | Q9ZGH3 |
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Entry name | RFFG_ECOLI | Q9EU31_SALCH | RMLB_SALTY | RMLB_STRMU | Q8GIP9_STRSU | Q9ZGH3_9ACTO |
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Activity | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. | dTDP-glucose = dTDP-4-dehydro-6-deoxy-D-glucose + H(2)O. |
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Subunit | Homodimer. |
| Homodimer. | Homodimer. |
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Subcellular location |
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Cofactor | NAD. | NAD (By similarity). | Binds 1 NAD ion per monomer. | Binds 1 NAD ion per monomer. | NAD (By similarity). | NAD (By similarity). |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[7] | Scheme 1, Fig.1, Fig.5 | 2 | [8] | Scheme 1, Scheme 2, Scheme 3 | 2 | [9] | Scheme 1, Scheme 2, Scheme 3 | 2 | [10] | Scheme 1, Scheme 3, Scheme 4, Scheme 5 | 3 | [12] | Fig.1 | 5 | [13] | Scheme 1, Scheme 2, Fig.4, Scheme 3 |
| [14] | Fig.4, p.88 | 3 | [15] | Scheme 1 |
| [16] | Scheme 2, p.2217-2220 |
| [17] | Fig.3, p.648-651 |
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references | [1] |
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PubMed ID | 7517391 |
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Journal | J Bacteriol |
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Year | 1994 |
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Volume | 176 |
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Pages | 4144-56 |
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Authors | Stevenson G, Neal B, Liu D, Hobbs M, Packer NH, Batley M, Redmond JW, Lindquist L, Reeves P |
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Title | Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster. |
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[2] |
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Comments | FUNCTION |
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Medline ID | 96032389 |
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PubMed ID | 7559340 |
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Journal | J Bacteriol |
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Year | 1995 |
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Volume | 177 |
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Pages | 5539-46 |
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Authors | Marolda CL, Valvano MA |
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Title | Genetic analysis of the dTDP-rhamnose biosynthesis region of the Escherichia coli VW187 (O7:K1) rfb gene cluster: identification of functional homologs of rfbB and rfbA in the rff cluster and correct location of the rffE gene. |
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Related UniProtKB | P27830 |
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[3] |
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PubMed ID | 9011374 |
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Journal | Carbohydr Res |
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Year | 1996 |
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Volume | 285 |
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Pages | 141-50 |
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Authors | Naundorf A, Klaffke W |
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Title | Substrate specificity of native dTDP-D-glucose-4,6-dehydratase: chemo-enzymatic syntheses of artificial and naturally occurring deoxy sugars. |
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[4] |
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PubMed ID | 10462438 |
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Journal | Arch Biochem Biophys |
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Year | 1999 |
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Volume | 369 |
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Pages | 30-41 |
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Authors | Essigmann B, Hespenheide BM, Kuhn LA, Benning C |
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Title | Prediction of the active-site structure and NAD(+) binding in SQD1, a protein essential for sulfolipid biosynthesis in Arabidopsis. |
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[5] |
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PubMed ID | 10358040 |
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Journal | J Biol Chem |
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Year | 1999 |
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Volume | 274 |
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Pages | 16933-9 |
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Authors | Yoshida Y, Nakano Y, Nezu T, Yamashita Y, Koga T |
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Title | A novel NDP-6-deoxyhexosyl-4-ulose reductase in the pathway for the synthesis of thymidine diphosphate-D-fucose. |
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[6] |
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PubMed ID | 10666612 |
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Journal | Acta Crystallogr D Biol Crystallogr |
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Year | 2000 |
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Volume | 56 |
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Pages | 222-5 |
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Authors | Allard ST, Giraud MF, Whitfield C, Messner P, Naismith JH |
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Title | The purification, crystallization and structural elucidation of dTDP-D-glucose 4,6-dehydratase (RmlB), the second enzyme of the dTDP-L-rhamnose synthesis pathway from Salmonella enterica serovar typhimurium. |
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[7] |
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PubMed ID | 11076501 |
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Journal | Biochemistry |
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Year | 2000 |
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Volume | 39 |
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Pages | 13633-40 |
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Authors | Gross JW, Hegeman AD, Vestling MM, Frey PA |
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Title | Characterization of enzymatic processes by rapid mix-quench mass spectrometry: the case of dTDP-glucose 4,6-dehydratase. |
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[8] |
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PubMed ID | 11478886 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 9187-95 |
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Authors | Gerratana B, Cleland WW, Frey PA |
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Title | Mechanistic roles of Thr134, Tyr160, and Lys 164 in the reaction catalyzed by dTDP-glucose 4,6-dehydratase. |
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[9] |
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PubMed ID | 11601973 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 12497-504 |
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Authors | Gross JW, Hegeman AD, Gerratana B, Frey PA |
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Title | Dehydration is catalyzed by glutamate-136 and aspartic acid-135 active site residues in Escherichia coli dTDP-glucose 4,6-dehydratase. |
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[10] |
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PubMed ID | 11380254 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 6598-610 |
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Authors | Hegeman AD, Gross JW, Frey PA |
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Title | Probing catalysis by Escherichia coli dTDP-glucose-4,6-dehydratase: identification and preliminary characterization of functional amino acid residues at the active site. |
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[11] |
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PubMed ID | 11553351 |
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Journal | Carbohydr Res |
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Year | 2001 |
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Volume | 335 |
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Pages | 23-32 |
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Authors | Amann S, Drager G, Rupprath C, Kirschning A, Elling L |
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Title | (Chemo)enzymatic synthesis of dTDP-activated 2,6-dideoxysugars as building blocks of polyketide antibiotics. |
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[12] |
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Comments | X-ray crystallography |
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PubMed ID | 11243820 |
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Journal | J Mol Biol |
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Year | 2001 |
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Volume | 307 |
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Pages | 283-95 |
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Authors | Allard ST, Giraud MF, Whitfield C, Graninger M, Messner P, Naismith JH |
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Title | The crystal structure of dTDP-D-Glucose 4,6-dehydratase (RmlB) from Salmonella enterica serovar Typhimurium, the second enzyme in the dTDP-l-rhamnose pathway. |
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Related PDB | 1g1a |
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[13] |
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PubMed ID | 11851427 |
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Journal | Biochemistry |
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Year | 2002 |
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Volume | 41 |
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Pages | 2797-804 |
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Authors | Hegeman AD, Gross JW, Frey PA |
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Title | Concerted and stepwise dehydration mechanisms observed in wild-type and mutated Escherichia coli dTDP-glucose 4,6-dehydratase. |
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[14] |
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PubMed ID | 11796113 |
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Journal | Structure (Camb) |
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Year | 2002 |
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Volume | 10 |
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Pages | 81-92 |
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Authors | Allard ST, Beis K, Giraud MF, Hegeman AD, Gross JW, Wilmouth RC, Whitfield C, Graninger M, Messner P, Allen AG, Maskell DJ, Naismith JH |
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Title | Toward a structural understanding of the dehydratase mechanism. |
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Related PDB | 1kep,1ker,1keu,1ket,1kew |
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[15] |
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PubMed ID | 14505409 |
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Journal | J Am Chem Soc |
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Year | 2003 |
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Volume | 125 |
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Pages | 11872-8 |
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Authors | Beis K, Allard ST, Hegeman AD, Murshudov G, Philp D, Naismith JH |
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Title | The structure of NADH in the enzyme dTDP-d-glucose dehydratase (RmlB). |
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Related PDB | 1oc2 |
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[16] |
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PubMed ID | 14570895 |
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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 | 2211-20 |
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Authors | Allard ST, Cleland WW, Holden HM |
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Title | High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae. |
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Related PDB | 1r66,1r6d |
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[17] |
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PubMed ID | 15493979 |
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Journal | Biochem Soc Trans |
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Year | 2004 |
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Volume | 32 |
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Pages | 647-54 |
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Authors | Naismith JH |
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Title | Chemical insights from structural studies of enzymes. |
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comments | This enzyme belongs to the Short-chain dehydrogenases/reductases (SDR). Although the catalytic site is slightly different, this enzyme is homologous to the GDP-mannose 4,6-dehydratases (EC 4.2.1.47, D00513 and D00543 in EzCatDB). This enzyme catalyzes reactions similar to those by its homologous enzymes (D00513 and D00543) (see [14]). According to the literature [14], [16] and [17], this enzyme catalyzes at least three reactions: oxidation of dTDP-glucose (hydride transfer from dTDP-glucose to nicotinamide), dehydration (elimination of a hydroxyl group from C6), and rereduction of C5-C6 double bond to methyl group (hydride transfer from nicotinamide to the intermediate). Taken together, this enzyme catalyzes the following reactions: (A) Hydride transfer from C4 atom of substrate to NAD, forming a 4-keto intermediate (I00091): (A0) Lys171 (of 1g1a) modulates the activity (or pKa) of Tyr167 via 2'-hydroxyl group of NAD, along with the N1 atom of the nicotinamide group in NAD, whereas Thr133 modulates the pKa of 4-hydroxyl oxygen of the substrate. (A1) Tyr167 acts as a general base to deprotonate the 4-hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4-carbon of the substrate to the C4 atom of the nicotinamide, forming the 4-keto intermediate (I00091). (B) Elimination of hydroxyl group from C6 of the intermediate, forming 4-keto-5,6-glucosen intermediate (I00092): (B1) Glu135 acts as a general base to deprotonate the C5 atom, possibly forming an enol/enolate transition-state. This transition-state might be stabilized by Tyr167 and Thr133. (B2) Asp134 acts as a general acid to protonate the O6 hydroxyl group, to release a water molecule, and to form the 4-keto-5,6-ene intermediate from the enol/enolate transition-state. (C) Hydride transfer from NADH to C6 atom of the intermediate (I00092): (C0) A slight rotation of the hexose ring of intermediate might be necessary for the reaction. Lys171 modulates the activity (or pKa) of Tyr167 via 2'-hydroxyl group of NAD, along with the N1 atom of the nicotinamide group in NAD. (C1) Hydride transfer from NADH to C6 atom of the hexose ring in the intermediate. Meanwhile, a general acid must protonate the C5 atom of the hexose. According to the literature [14] and [17], Tyr167 seems to play a role as a general acid. (Thr133 might assist Tyr167 as a general acid, probably acting as a proton shuttle as in the homologous enzyme.)
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created | updated |
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2004-06-07 | 2011-06-16 |
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