DB code: D00601

RLCP classification 9.5010.536200.8011 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
3.90.25.10 : UDP-galactose 4-epimerase; domain 1
E.C. 1.1.1.133
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
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 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109
3.90.25.10 : UDP-galactose 4-epimerase; domain 1 D00513 D00604 D00262 D00274 D00275

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P26392 dTDP-4-dehydrorhamnose reductase
EC 1.1.1.133
dTDP-4-keto-L-rhamnose reductase
dTDP-6-deoxy-L-mannose dehydrogenase
dTDP-L-rhamnose synthetase
NP_461041.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF04321 (RmlD_sub_bind)
[Graphical View]
Q9F7K7
DTDP-6-deoxy-L-mannose-dehydrogenase
PF04321 (RmlD_sub_bind)
[Graphical View]
Q97GQ1
DTDP-4-dehydrorhamnose reductase, rfbD ortholog
NP_348931.1 (Protein)
NC_003030.1 (DNA/RNA sequence)
PF04321 (RmlD_sub_bind)
[Graphical View]
Q96Z61
273aa long hypothetical dTDP-4-dehydrorhamnose reductase
NP_377956.1 (Protein)
NC_003106.2 (DNA/RNA sequence)
PF04321 (RmlD_sub_bind)
[Graphical View]

KEGG enzyme name
dTDP-4-dehydrorhamnose reductase
dTDP-4-keto-L-rhamnose reductase
Reductase, thymidine diphospho-4-ketorhamnose
dTDP-4-ketorhamnose reductase
TDP-4-keto-rhamnose reductase
Thymidine diphospho-4-ketorhamnose reductase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P26392 RFBD_SALTY dTDP-6-deoxy-L-mannose + NADP(+) = dTDP-4-dehydro-6-deoxy-L-mannose + NADPH.
Q9F7K7 Q9F7K7_SALCH
Q97GQ1 Q97GQ1_CLOAB
Q96Z61 Q96Z61_SULTO

KEGG Pathways
Map code Pathways E.C.
MAP00521 Streptomycin biosynthesis
MAP00523 Polyketide sugar unit biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00688 C00005 C00080 C03319 C00006
E.C.
Compound dTDP-4-dehydro-6-deoxy-L-mannose NADPH H+ dTDP-6-deoxy-L-mannose NADP+
Type amide group,carbohydrate,nucleotide amide group,amine group,nucleotide others amide group,carbohydrate,nucleotide amide group,amine group,nucleotide
ChEBI 45868
 45868
 		16474
 16474
 		15378
 15378
 		15774
 15774
 		18009
 18009
PubChem 443211
 443211
 		5884
 5884
 		1038
 1038
 		121966
 121966
 		5886
 5886
1kbzA01 Unbound Unbound Unbound Unbound
1kc1A01 Unbound Unbound Unbound Bound:NDP
1kc3A01 Unbound Bound:NDP Bound:TRH Unbound
1kc0A01 Unbound Unbound Unbound Bound:NDP
1n2sA01 Unbound Analogue:NAD Unbound Unbound
1vl0A01 Unbound Unbound Unbound Analogue:NAI
1vl0B01 Unbound Unbound Unbound Analogue:NAI
1vl0C01 Unbound Unbound Unbound Analogue:NAI
2ggsA01 Unbound Unbound Unbound Bound:NDP
2ggsB01 Unbound Unbound Unbound Bound:NDP
1kbzA02 Unbound Unbound Unbound Unbound
1kc1A02 Unbound Unbound Unbound Unbound
1kc3A02 Unbound Unbound Unbound Unbound
1kc0A02 Unbound Unbound Unbound Unbound
1n2sA02 Unbound Unbound Unbound Unbound
1vl0A02 Unbound Unbound Unbound Unbound
1vl0B02 Unbound Unbound Unbound Unbound
1vl0C02 Unbound Unbound Unbound Unbound
2ggsA02 Unbound Unbound Unbound Unbound
2ggsB02 Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4], [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1kbzA01 THR 104;TYR 128;LYS 132
1kc1A01 THR 104;TYR 128;LYS 132
1kc3A01 THR 104;TYR 128;LYS 132
1kc0A01 THR 104;TYR 128;LYS 132
1n2sA01 THR 104;TYR 128;LYS 132
1vl0A01 THR 101;TYR 125;LYS 129
1vl0B01 THR 101;TYR 125;LYS 129
1vl0C01 THR 101;TYR 125;LYS 129
2ggsA01 THR 107;TYR 130;LYS 134
2ggsB01 THR 107;TYR 130;LYS 134
1kbzA02
1kc1A02
1kc3A02
1kc0A02
1n2sA02
1vl0A02
1vl0B02
1vl0C02
2ggsA02
2ggsB02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.13101
[7]
Fig.6, p.782-783
[8]
Fig.4, p.648-650

References
[1]
Resource
Comments
Medline ID
PubMed ID 7742302
Journal Biochemistry
Year 1995
Volume 34
Pages 6003-13
Authors Jornvall H, Persson B, Krook M, Atrian S, Gonzalez-Duarte R, Jeffery J, Ghosh D
Title Short-chain dehydrogenases/reductases (SDR).
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID
PubMed ID 8805577
Journal Structure
Year 1996
Volume 4
Pages 905-15
Authors Breton R, Housset D, Mazza C, Fontecilla-Camps JC
Title The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors.
Related PDB 1fds 1fdt
Related UniProtKB P14061
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY
Medline ID
PubMed ID 9271498
Journal Biochemistry
Year 1997
Volume 36
Pages 10675-84
Authors Liu Y, Thoden JB, Kim J, Berger E, Gulick AM, Ruzicka FJ, Holden HM, Frey PA
Title Mechanistic roles of tyrosine 149 and serine 124 in UDP-galactose 4-epimerase from Escherichia coli.
Related PDB 1kvu
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NAD(+) AND UDP-GLUCOSE.
Medline ID
PubMed ID 10557279
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 13097-102
Authors Mulichak AM, Theisen MJ, Essigmann B, Benning C, Garavito RM
Title Crystal structure of SQD1, an enzyme involved in the biosynthesis of the plant sulfolipid headgroup donor UDP-sulfoquinovose.
Related PDB 1qrr
Related UniProtKB O48917
[5]
Resource
Comments
Medline ID
PubMed ID 11478886
Journal Biochemistry
Year 2001
Volume 40
Pages 9187-95
Authors Gerratana B, Cleland WW, Frey PA
Title Mechanistic roles of Thr134, Tyr160, and Lys 164 in the reaction catalyzed by dTDP-glucose 4,6-dehydratase.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY
Medline ID
PubMed ID 11243820
Journal J Mol Biol
Year 2001
Volume 307
Pages 283-95
Authors Allard ST, Giraud MF, Whitfield C, Graninger M, Messner P, Naismith JH
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.
Related PDB 1g1a
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY
Medline ID
PubMed ID 12057193
Journal Structure
Year 2002
Volume 10
Pages 773-86
Authors Blankenfeldt W, Kerr ID, Giraud MF, McMiken HJ, Leonard G, Whitfield C, Messner P, Graninger M, Naismith JH
Title Variation on a theme of SDR. dTDP-6-deoxy-L- lyxo-4-hexulose reductase (RmlD) shows a new Mg2+-dependent dimerization mode.
Related PDB 1kbz 1kc1 1kc3 1kc0 1n2s
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 15493979
Journal Biochem Soc Trans
Year 2004
Volume 32
Pages 647-54
Authors Naismith JH
Title Chemical insights from structural studies of enzymes.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the Short-chain dehydrogenases/reductases (SDR) (literature [1] & [7]).
This enzyme is homologous to Estradiol 17-beta-dehydrogenase 1 (EC=1.1.1.62, S00327 in EzCatDB), UDP-glucose 4-epimerase (EC=5.1.3.2, D00274) and dTDP-glucose 4,6-dehydratase (EC=4.2.1.46, D00262).
Although this enzyme requires Mg2+ for full activity, Mg2+ is necessary for its dimerization rather than its catalysis (see [7]).
According to the literature [7] and [8], the reaction of this enzyme proceeds as follows:
(0) Lys132 (of 1kbz) modulates the activity (or pKa) of Tyr128 via 2'-hydroxyl group of NADPH, along with the N1 atom of the nicotinamide group in NAD, whereas Thr104 modulates the pKa of 4-carbonyl oxygen of the substrate.
(1) Tyr128 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate.

Created Updated
2010-05-07 2011-06-01