DB code: D00544

RLCP classification 9.5010.536200.8011 : Hydride transfer
9.1050.440000.8011 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
3.90.25.10 : UDP-galactose 4-epimerase; domain 1
E.C. 5.1.3.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q81K34
UDP-glucose 4-epimerase
EC 5.1.3.2
NP_847665.1 (Protein)
NC_003997.3 (DNA/RNA sequence)
YP_022172.1 (Protein)
NC_007530.2 (DNA/RNA sequence)
YP_031353.1 (Protein)
NC_005945.1 (DNA/RNA sequence)
PF01370 (Epimerase)
PF13950 (Epimerase_Csub)
[Graphical View]

KEGG enzyme name
UDP-glucose 4-epimerase
UDP-galactose 4-epimerase
uridine diphosphoglucose epimerase
galactowaldenase
UDPG-4-epimerase
uridine diphosphate galactose 4-epimerase
uridine diphospho-galactose-4-epimerase
UDP-glucose epimerase
UDP-galactose 4-epimerase
4-epimerase
UDPG-4-epimerase
uridine diphosphoglucose 4-epimerase
uridine diphosphate glucose 4-epimerase
UDP-D-galactose 4-epimerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q81K34 Q81K34_BACAN

KEGG Pathways
Map code Pathways E.C.
MAP00520 Nucleotide sugars metabolism
MAP00052 Galactose metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00003 C00029 C00052 I00016
E.C.
Compound NAD+ UDP-glucose UDP-galactose UDP-4-ketohexopyranose
Type amide group,amine group,nucleotide amide group,carbohydrate,nucleotide amide group,carbohydrate,nucleotide
ChEBI 15846
46229
PubChem 5893
8629
23724458
2c20A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20E01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20F01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound
2c20A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2c20B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2c20C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2c20D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2c20E02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2c20F02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [22], [31], [35]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2c20A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20E01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20F01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 118;TYR 142;LYS 146
2c20A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2c20B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2c20C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2c20D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2c20E02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2c20F02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.2, p.135-136
[6]
Fig.2, p.373
[7]
p.13227-13230
[8]
p.13235-13236
[11]
p.5139-5143
[12]
Fig.10, p.2156-2159
[13]
Scheme 1, Scheme 2, Scheme 3, p.10682-10683
[14]
p.10694-10695
[15]
Scheme 1, p.6294-6295, p.6302-6303
[18]
Scheme 1, p.11474-11477
[20]
Scheme 1, p.5697-5700
[22]
Scheme 1, Fig.4, p.6703-6705
[23]
Scheme 1, p.9187-9188
[24]
Scheme 1, Fig.6, p.11284-11286
[29]
p.250
[30]
Scheme 1
[31]
p.177-179
[32]
Fig.2, p.13371
[33]
Scheme 2, p.3065-3066
[35]
p.832-833

References
[1]
Resource
Comments
Medline ID
PubMed ID 3061645
Journal Carbohydr Res
Year 1988
Volume 179
Pages 289-99
Authors Kaca W, de Jongh-Leuvenink J, Zahringer U, Rietschel ET, Brade H, Verhoef J, Sinnwell V
Title Isolation and chemical analysis of 7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose as a constituent of the lipopolysaccharides of the UDP-galactose epimerase-less mutant J-5 of Escherichia coli and Vibrio cholerae.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2659075
Journal Biochemistry
Year 1989
Volume 28
Pages 2645-54
Authors Konopka JM, Halkides CJ, Vanhooke JL, Gorenstein DG, Frey PA
Title UDP-galactose 4-epimerase. Phosphorus-31 nuclear magnetic resonance analysis of NAD+ and NADH bound at the active site.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2008433
Journal Proteins
Year 1991
Volume 9
Pages 135-42
Authors Bauer AJ, Rayment I, Frey PA, Holden HM
Title The isolation, purification, and preliminary crystallographic characterization of UDP-galactose-4-epimerase from Escherichia coli.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1601848
Journal J Biol Chem
Year 1992
Volume 267
Pages 11714-20
Authors Bhattacharjee H, Bhaduri A
Title Distinct functional roles of two active site thiols in UDPglucose 4-epimerase from Kluyveromyces fragilis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1297789
Journal J Nutr Sci Vitaminol (Tokyo)
Year 1992
Volume Spec No
Pages 461-4
Authors Frey PA, Bauer AJ, Vanhooke JL, Konopka JM, Rayment I, Holden HM
Title Chemical spectroscopic and crystallographic studies of UDP-galactose 4-epimerase from Escherichia coli.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 92253563
PubMed ID 1579570
Journal Proteins
Year 1992
Volume 12
Pages 372-81
Authors Bauer AJ, Rayment I, Frey PA, Holden HM
Title The molecular structure of UDP-galactose 4-epimerase from Escherichia coli determined at 2.5 A resolution.
Related PDB 1udp
Related UniProtKB P09147
[7]
Resource
Comments
Medline ID
PubMed ID 8241177
Journal Biochemistry
Year 1993
Volume 32
Pages 13220-30
Authors Burke JR, Frey PA
Title The importance of binding energy in catalysis of hydride transfer by UDP-galactose 4-epimerase: a 13C and 15N NMR and kinetic study.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8241178
Journal Biochemistry
Year 1993
Volume 32
Pages 13231-6
Authors Swanson BA, Frey PA
Title Identification of lysine 153 as a functionally important residue in UDP-galactose 4-epimerase from Escherichia coli.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8652544
Journal Biochemistry
Year 1996
Volume 35
Pages 7615-20
Authors Liu Y, Vanhooke JL, Frey PA
Title UDP-galactose 4-epimerase: NAD+ content and a charge-transfer band associated with the substrate-induced conformational transition.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 96180680
PubMed ID 8611559
Journal Biochemistry
Year 1996
Volume 35
Pages 2557-66
Authors Thoden JB, Frey PA, Holden HM
Title Crystal structures of the oxidized and reduced forms of UDP-galactose 4-epimerase isolated from Escherichia coli.
Related PDB 1nah 1nai
Related UniProtKB P09147
[11]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8611497
Journal Biochemistry
Year 1996
Volume 35
Pages 5137-44
Authors Thoden JB, Frey PA, Holden HM
Title Molecular structure of the NADH/UDP-glucose abortive complex of UDP-galactose 4-epimerase from Escherichia coli: implications for the catalytic mechanism.
Related PDB 1xel
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 97084800
PubMed ID 8931134
Journal Protein Sci
Year 1996
Volume 5
Pages 2149-61
Authors Thoden JB, Frey PA, Holden HM
Title High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol.
Related PDB 2udp
Related UniProtKB P09147
[13]
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
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF SER-124 MUTANTS.
Medline ID 97419132
PubMed ID 9271499
Journal Biochemistry
Year 1997
Volume 36
Pages 10685-95
Authors Thoden JB, Gulick AM, Holden HM
Title Molecular structures of the S124A, S124T, and S124V site-directed mutants of UDP-galactose 4-epimerase from Escherichia coli.
Related PDB 1kvq 1kvr 1kvs 1kvt
Related UniProtKB P09147
[15]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID 97317070
PubMed ID 9174344
Journal Biochemistry
Year 1997
Volume 36
Pages 6294-304
Authors Thoden JB, Hegeman AD, Wesenberg G, Chapeau MC, Frey PA, Holden HM
Title Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from Escherichia coli.
Related PDB 1uda 1udb 1udc
Related UniProtKB P09147
[16]
Resource
Comments
Medline ID
PubMed ID 9119006
Journal Eur J Biochem
Year 1997
Volume 244
Pages 407-13
Authors Dutta S, Maiti NR, Bhattacharyya D
Title Reversible folding of UDP-galactose 4-epimerase from Escherichia coli.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9224707
Journal FEBS Lett
Year 1997
Volume 409
Pages 449-51
Authors Nayar S, Bhattacharyya D
Title UDP-galactose 4-epimerase from Escherichia coli: existence of a catalytic monomer.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANTS.
Medline ID 98376428
PubMed ID 9708982
Journal Biochemistry
Year 1998
Volume 37
Pages 11469-77
Authors Thoden JB, Holden HM
Title Dramatic differences in the binding of UDP-galactose and UDP-glucose to UDP-galactose 4-epimerase from Escherichia coli.
Related PDB 1a9y 1a9z
Related UniProtKB P09147
[19]
Resource
Comments
Medline ID
PubMed ID 10329648
Journal J Biol Chem
Year 1999
Volume 274
Pages 14573-8
Authors Bhattacharyya U, Dhar G, Bhaduri A
Title An arginine residue is essential for stretching and binding of the substrate on UDP-glucose-4-epimerase from Escherichia coli. Use of a stacked and quenched uridine nucleotide fluorophore as probe.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
Medline ID 20263487
PubMed ID 10801319
Journal Biochemistry
Year 2000
Volume 39
Pages 5691-701
Authors Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM
Title Crystallographic evidence for Tyr 157 functioning as the active site base in human UDP-galactose 4-epimerase.
Related PDB 1ek5 1ek6
Related UniProtKB Q14376
[21]
Resource
Comments
Medline ID
PubMed ID 11437350
Journal Arch Biochem Biophys
Year 2001
Volume 391
Pages 188-96
Authors Barat B, Bhattacharyya D
Title UDP-galactose 4-epimerase from Escherichia coli: formation of catalytic site during reversible folding.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11380265
Journal Biochemistry
Year 2001
Volume 40
Pages 6699-705
Authors Berger E, Arabshahi A, Wei Y, Schilling JF, Frey PA
Title Acid-base catalysis by UDP-galactose 4-epimerase: correlations of kinetically measured acid dissociation constants with thermodynamic values for tyrosine 149.
Related PDB
Related UniProtKB
[23]
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
[24]
Resource
Comments
Medline ID
PubMed ID 11551228
Journal Biochemistry
Year 2001
Volume 40
Pages 11279-87
Authors Wei Y, Lin J, Frey PA
Title 13C NMR analysis of electrostatic interactions between NAD+ and active site residues of UDP-galactose 4-epimerase: implications for the activation induced by uridine nucleotides.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11726498
Journal EMBO J
Year 2001
Volume 20
Pages 6619-26
Authors Stammers DK, Ren J, Leslie K, Nichols CE, Lamb HK, Cocklin S, Dodds A, Hawkins AR
Title The structure of the negative transcriptional regulator NmrA reveals a structural superfamily which includes the short-chain dehydrogenase/reductases.
Related PDB
Related UniProtKB
[26]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF VARIANT EDG MET-94.
Medline ID 21282994
PubMed ID 11279193
Journal J Biol Chem
Year 2001
Volume 276
Pages 20617-23
Authors Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM
Title Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase.
Related PDB 1i3k 1i3l 1i3m 1i3n
Related UniProtKB Q14376
[27]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11279032
Journal J Biol Chem
Year 2001
Volume 276
Pages 15131-6
Authors Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM
Title Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site.
Related PDB 1hzj
Related UniProtKB
[28]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12019271
Journal J Biol Chem
Year 2002
Volume 277
Pages 27528-34
Authors Thoden JB, Henderson JM, Fridovich-Keil JL, Holden HM
Title Structural analysis of the Y299C mutant of Escherichia coli UDP-galactose 4-epimerase. Teaching an old dog new tricks.
Related PDB 1lrj 1lrk 1lrl
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12604210
Journal Chem Biol Interact
Year 2003
Volume 143-144
Pages 247-53
Authors Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, Shafqat J, Nordling E, Kallberg Y, Persson B, Jornvall H
Title Short-chain dehydrogenases/reductases (SDR): the 2002 update.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 12642575
Journal J Biol Chem
Year 2003
Volume 278
Pages 20874-81
Authors Koropatkin NM, Liu HW, Holden HM
Title High resolution x-ray structure of tyvelose epimerase from Salmonella typhi.
Related PDB
Related UniProtKB
[31]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12615316
Journal Mol Biochem Parasitol
Year 2003
Volume 126
Pages 173-80
Authors Shaw MP, Bond CS, Roper JR, Gourley DG, Ferguson MA, Hunter WN
Title High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4'-epimerase: a potential target for structure-based development of novel trypanocides.
Related PDB 1gy8
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 15491143
Journal Biochemistry
Year 2004
Volume 43
Pages 13370-9
Authors Gatzeva-Topalova PZ, May AP, Sousa MC
Title Crystal structure of Escherichia coli ArnA (PmrI) decarboxylase domain. A key enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 15023057
Journal Biochemistry
Year 2004
Volume 43
Pages 3057-67
Authors Vogan EM, Bellamacina C, He X, Liu HW, Ringe D, Petsko GA
Title Crystal structure at 1.8 A resolution of CDP-D-glucose 4,6-dehydratase from Yersinia pseudotuberculosis.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 15175331
Journal J Biol Chem
Year 2004
Volume 279
Pages 32796-803
Authors Schulz JM, Watson AL, Sanders R, Ross KL, Thoden JB, Holden HM, Fridovich-Keil JL
Title Determinants of function and substrate specificity in human UDP-galactose 4'-epimerase.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 16946458
Journal Acta Crystallograph Sect F Struct Biol Cryst Commun
Year 2006
Volume 62
Pages 829-34
Authors Alphey MS, Burton A, Urbaniak MD, Boons GJ, Ferguson MA, Hunter WN
Title Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose.
Related PDB 2cnb
Related UniProtKB

Comments
This enzyme is a homologous enzyme to the counterpart enzymes from E. coli, trypanosoma and human (D00274 in EzCatDB).
This enzyme is a distant homologue of the short-chain dehydrogenase/reductase (SDR) superfamily, which includes Drosophia alcohol dehydrogenase (S00319 in EzCatDB). Those homologous enzymes have got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. At the position of the catalytic serine residue, this enzyme has got threonine residue, which seems to play the same role as the catalytic serine.
According to the literature [22], [31] and [35], this enzyme catalyzes the following reactions:
(A) Hydride transfer from C4' atom of substrate to NAD+, forming 4-keto intermediate and NADH.
This reaction mechanism must be the same as that by Drosophia alcohol dehydrogenase.
(X) Rotation or conformation change of the intermediate.
(B) Hydride transfer from NADH to C4' atom of the 4-ketose intermediate, recovering NAD+.
This reaction mechanism also must be the same as the reverse reaction by Drosophia alcohol dehydrogenase.

Created Updated
2011-07-04 2011-07-05