DB code: T00227

RLCP classification 9.1050.439980.119 : Hydride transfer
4.501.3944060.57 : Addition
9.1050.584160.119 : Hydride transfer
1.14.800.129 : Hydrolysis
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
3.40.50.720 : Rossmann fold
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 Catalytic domain
E.C. 1.1.1.22
CSA 1dli
M-CSA 1dli
MACiE M0092

CATH domain Related DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 D00007 D00012 D00603 T00002
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 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P0C0F4 UDP-glucose 6-dehydrogenase
UDP-Glc dehydrogenase
UDP-GlcDH
UDPGDH
EC 1.1.1.22
PF00984 (UDPG_MGDP_dh)
PF03720 (UDPG_MGDP_dh_C)
PF03721 (UDPG_MGDP_dh_N)
[Graphical View]

KEGG enzyme name
UDP-glucose 6-dehydrogenase
UDP-glucose dehydrogenase
uridine diphosphoglucose dehydrogenase
UDPG dehydrogenase
UDPG:NAD oxidoreductase
UDP-alpha-D-glucose:NAD oxidoreductase
UDP-glucose:NAD+ oxidoreductase
uridine diphosphate glucose dehydrogenase
UDP-D-glucose dehydrogenase
uridine diphosphate D-glucose dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0C0F4 UDG_STRPY UDP-glucose + 2 NAD(+) + H(2)O = UDP- glucuronate + 2 NADH.

KEGG Pathways
Map code Pathways E.C.
MAP00040 Pentose and glucuronate interconversions
MAP00053 Ascorbate and aldarate metabolism
MAP00500 Starch and sucrose metabolism
MAP00520 Nucleotide sugars metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00029 C00003 C00001 C00167 C00004 I00106 I00107 I00108
E.C.
Compound UDP-glucose NAD+ H2O UDP-glucuronate NADH UDP-6-dehydro-glucose Protein [UDP-6-S-D-glucose]-L-cysteine Protein [UDP-6-S-6-dehydro-D-glucose]-L-cysteine
Type amide group,carbohydrate,nucleotide amide group,amine group,nucleotide H2O amide group,carbohydrate,carboxyl group,nucleotide amide group,amine group,nucleotide
ChEBI 46229
 46229
 		15846
 15846
 		15377
 15377
 		17200
 17200
 		16908
 16908
PubChem 8629
 8629
 		5893
 5893
 		22247451
 962
 22247451
 962
 		17473
 17473
 		439153
 439153
1dliA01 Analogue:UDX Bound:NAD Unbound Unbound Unbound Unbound Unbound
1dljA01 Unbound Unbound Bound:UGA Bound:NAI Unbound Unbound Unbound
1dliA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dljA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dliA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dljA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P0C0F4

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dliA01 THR 118;GLU 145;LYS 204
1dljA01 THR 118;GLU 145;LYS 204
1dliA02
1dljA02
1dliA03 ASN 208;CYS 260;LYS 263;ASP 264
1dljA03 ASN 208;;LYS 263;ASP 264 mutant C260S

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.4
[11]
Scheme 1, Fig.8, p.7020-7022
[13]
p.18-20, Fig.1, Fig.3
[14]
p.1380-1382, Fig.2

References
[1]
Resource
Comments
Medline ID
PubMed ID 192218
Journal Biochem J
Year 1977
Volume 162
Pages 267-79
Authors Dalessandro G, Northcote DH
Title Changes in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in sycamore and poplar.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 557038
Journal J Biol Chem
Year 1977
Volume 252
Pages 1320-6
Authors Ordman AB, Kirkwood S
Title Mechanism of action of uridine diphoglucose dehydrogenase. Evidence for an essential lysine residue at the active site.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 697744
Journal Biochem J
Year 1978
Volume 173
Pages 701-4
Authors Franzen JS, Marchetti P, Ishman R, Ashcom J
Title Half-sites oxidation of bovine liver uridine diphosphate glucose dehydrogenase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 42793
Journal J Rheumatol
Year 1979
Volume 6
Pages 489-96
Authors Ross GT, Marsh JM, Roback DW
Title Uridine diphosphate glucose dehydrogenase in normal human synovial cells in culture.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7470452
Journal Biochemistry
Year 1980
Volume 19
Pages 6080-9
Authors Franzen JS, Marchetti PS, Feingold DS
Title Resonance energy transfer between catalytic sites of bovine liver uridine diphosphoglucose dehydrogenase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7407191
Journal Biochim Biophys Acta
Year 1980
Volume 614
Pages 242-55
Authors Franzen JS, Ashcom J, Marchetti P, Cardamone JJ Jr, Feingold DS
Title Induced versus pre-existing asymmetry models for the half-of-the-sites reactivity effect in bovine liver uridine diphosphoglucose dehydrogenase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 6896145
Journal Biochem J
Year 1981
Volume 199
Pages 599-602
Authors Franzen B, Carrubba C, Feingold DS, Ashcom J, Franzen JS
Title Amino acid sequence of the tryptic peptide containing the catalytic-site thiol group of bovine liver uridine diphosphate glucose dehydrogenase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 6882768
Journal Biochim Biophys Acta
Year 1983
Volume 746
Pages 146-53
Authors Franzen JS, Marchetti PS, Lockhart AH, Feingold DS
Title Special effects of UDP-sugar binding to bovine liver uridine diphosphoglucose dehydrogenase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7920253
Journal Protein Sci
Year 1994
Volume 3
Pages 1074-80
Authors Hempel J, Perozich J, Romovacek H, Hinich A, Kuo I, Feingold DS
Title UDP-glucose dehydrogenase from bovine liver: primary structure and relationship to other dehydrogenases.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8938413
Journal Plant Physiol
Year 1996
Volume 112
Pages 1127-34
Authors Tenhaken R, Thulke O
Title Cloning of an enzyme that synthesizes a key nucleotide-sugar precursor of hemicellulose biosynthesis from soybean: UDP-glucose dehydrogenase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10841783
Journal Biochemistry
Year 2000
Volume 39
Pages 7012-23
Authors Campbell RE, Mosimann SC, van De Rijn I, Tanner ME, Strynadka NC
Title The first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation.
Related PDB 1dli 1dlj
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12031484
Journal Biochim Biophys Acta
Year 2002
Volume 1576
Pages 53-8
Authors Johansson H, Sterky F, Amini B, Lundeberg J, Kleczkowski LA
Title Molecular cloning and characterization of a cDNA encoding poplar UDP-glucose dehydrogenase, a key gene of hemicellulose/pectin formation.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 14686915
Journal Eur J Biochem
Year 2004
Volume 271
Pages 14-22
Authors Ge X, Penney LC, van de Rijn I, Tanner ME
Title Active site residues and mechanism of UDP-glucose dehydrogenase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 20863317
Journal Biochem Soc Trans
Year 2010
Volume 38
Pages 1378-85
Authors Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B
Title UDP-glucose dehydrogenase: structure and function of a potential drug target.
Related PDB
Related UniProtKB

Comments
This enzyme is homologous to GDP-mannose 6-dehydrogenase (EC=1.1.1.132, T00408 in EzCatDB), although their second domains are classified into different categories in the structural classification (CATH).
According to the literature [11] and the reaction mechanism of T00408, this enzyme catalyzes the following reactions:
(A) Hydride transfer from C6' atom of UDP-glucose to nicotinamide of NAD, forming an aldehyde intermediate, UDP-6-dehydro-D-glucose (I00106):
(A1) Lys204 acts as a general base to deprotonate the hydroxyl oxygen, whereas hydride transfer occurs from C6' atom to nicotinamide of NAD. (Here, instead of Lys204, Asp264' (from the adjacent chain) may act as a general base to deprotonate the C6' atom through a water, with Thr118 interacting with C6' through the same water molecule. Thr118 may modulate the pKa of C6' atom through the water, and Asn208 may modulate the pKa of Asp264'.)
(B) Addition of Cys260 to carbonyl C6' atom of the aldehyde intermediate, forming the second thiohemiacetal intermediate (I00107):
(B0) Lys263' (from adjacent chain) and (a positive charged dipole of) a nearby alpha-helix modulates and lowers the pKa of Cys260' to activate the nucleophilic residue.
(B1) The activated Cys260' makes a nucleophilic attack on the aldehyde intermediate.
(B2) Lys204 and Asp264'/Thr118 may stabilize the oxyanion produced by the addition reaction.
(C) Hydride transfer from C6' atom of the thiohemiacetal intermediate to nicotinamide of NAD, forming the third thioester intermediate (I00108):
(C0) Lys204 and Asp264'/Thr118 may stabilize the oxyanion of the intermediate. (Asp264' and Thr118 interact with the oxyanion through a water.)
(C1) Collapse of the oxyanion leads to the hydride transfer from C6' atom to nicotinamide of NAD, forming the thioester intermediate.
(D) Hydrolysis of the thioester intermediate:
(D1) Glu145 acts as a general base to deprotonate and activate a water molecule.
(D2) The activated water makes a nucleophilic attack on the thioester group, leading to an oxyanion transition-state. The oxyanion is stabilized by Lys204 and Asp264'/Thr118. (Asp264' and Thr118 interact with the oxyanion through a water.)
(D3) The oxyanion collapses and Cys260 is released.

Created Updated
2004-03-24 2011-09-14