EzCatDB: T00227

DB codeT00227
RLCP classification4.501.3944060.57
1.14.800.129
CATH domainDomain 13.40.50.720Catalytic domain
Domain 23.40.50.720
Domain 31.10.1040.10Catalytic domain
E.C.1.1.1.22
CSA1dli
MACiEM0092

CATH domainRelated DB codes (homologues)
1.10.1040.10D00007,D00012,D00603,T00002
3.40.50.720S00543,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

Enzyme Name
Swiss-protKEGG

P0C0F4
Protein nameUDP-glucose 6-dehydrogenaseUDP-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
SynonymsUDP-Glc dehydrogenase
UDP-GlcDH
UDPGDH
EC 1.1.1.22

KEGG pathways
MAP codePathways
MAP00040Pentose and glucuronate interconversions
MAP00053Ascorbate and aldarate metabolism
MAP00500Starch and sucrose metabolism
MAP00520Nucleotide sugars metabolism

Swiss-prot:Accession NumberP0C0F4
Entry nameUDG_STRPY
ActivityUDP-glucose + 2 NAD(+) + H(2)O = UDP- glucuronate + 2 NADH.
Subunit
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00029C00003C00001C00167C00004I00106I00107I00108
CompoundUDP-glucoseNAD+H2OUDP-glucuronateNADHUDP-6-dehydro-glucoseProtein [UDP-6-S-D-glucose]-L-cysteineProtein [UDP-6-S-6-dehydro-D-glucose]-L-cysteine
Typeamide group,carbohydrate,nucleotideamide group,amine group,nucleotideH2Oamide group,carbohydrate,carboxyl group,nucleotideamide group,amine group,nucleotide


1dliA01Analogue:UDXBound:NAD
UnboundUnboundUnboundUnboundUnbound
1dljA01UnboundUnbound
Bound:UGABound:NAIUnboundUnboundUnbound
1dliA02UnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1dljA02UnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1dliA03UnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1dljA03UnboundUnbound
UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P0C0F4
pdbCatalytic residuescomment
1dliA01THR 118;GLU 145;LYS 204

1dljA01THR 118;GLU 145;LYS 204

1dliA02

1dljA02

1dliA03ASN 208;CYS 260;LYS 263;ASP 264

1dljA03ASN 208;       ;LYS 263;ASP 264
mutant C260S

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID192218
JournalBiochem J
Year1977
Volume162
Pages267-79
AuthorsDalessandro G, Northcote DH
TitleChanges in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in sycamore and poplar.
[2]
PubMed ID557038
JournalJ Biol Chem
Year1977
Volume252
Pages1320-6
AuthorsOrdman AB, Kirkwood S
TitleMechanism of action of uridine diphoglucose dehydrogenase. Evidence for an essential lysine residue at the active site.
[3]
PubMed ID697744
JournalBiochem J
Year1978
Volume173
Pages701-4
AuthorsFranzen JS, Marchetti P, Ishman R, Ashcom J
TitleHalf-sites oxidation of bovine liver uridine diphosphate glucose dehydrogenase.
[4]
PubMed ID42793
JournalJ Rheumatol
Year1979
Volume6
Pages489-96
AuthorsRoss GT, Marsh JM, Roback DW
TitleUridine diphosphate glucose dehydrogenase in normal human synovial cells in culture.
[5]
PubMed ID7470452
JournalBiochemistry
Year1980
Volume19
Pages6080-9
AuthorsFranzen JS, Marchetti PS, Feingold DS
TitleResonance energy transfer between catalytic sites of bovine liver uridine diphosphoglucose dehydrogenase.
[6]
PubMed ID7407191
JournalBiochim Biophys Acta
Year1980
Volume614
Pages242-55
AuthorsFranzen JS, Ashcom J, Marchetti P, Cardamone JJ Jr, Feingold DS
TitleInduced versus pre-existing asymmetry models for the half-of-the-sites reactivity effect in bovine liver uridine diphosphoglucose dehydrogenase.
[7]
PubMed ID6896145
JournalBiochem J
Year1981
Volume199
Pages599-602
AuthorsFranzen B, Carrubba C, Feingold DS, Ashcom J, Franzen JS
TitleAmino acid sequence of the tryptic peptide containing the catalytic-site thiol group of bovine liver uridine diphosphate glucose dehydrogenase.
[8]
PubMed ID6882768
JournalBiochim Biophys Acta
Year1983
Volume746
Pages146-53
AuthorsFranzen JS, Marchetti PS, Lockhart AH, Feingold DS
TitleSpecial effects of UDP-sugar binding to bovine liver uridine diphosphoglucose dehydrogenase.
[9]
PubMed ID7920253
JournalProtein Sci
Year1994
Volume3
Pages1074-80
AuthorsHempel J, Perozich J, Romovacek H, Hinich A, Kuo I, Feingold DS
TitleUDP-glucose dehydrogenase from bovine liver: primary structure and relationship to other dehydrogenases.
[10]
PubMed ID8938413
JournalPlant Physiol
Year1996
Volume112
Pages1127-34
AuthorsTenhaken R, Thulke O
TitleCloning of an enzyme that synthesizes a key nucleotide-sugar precursor of hemicellulose biosynthesis from soybean: UDP-glucose dehydrogenase.
[11]
PubMed ID10841783
JournalBiochemistry
Year2000
Volume39
Pages7012-23
AuthorsCampbell RE, Mosimann SC, van De Rijn I, Tanner ME, Strynadka NC
TitleThe first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation.
Related PDB1dli,1dlj
[12]
PubMed ID12031484
JournalBiochim Biophys Acta
Year2002
Volume1576
Pages53-8
AuthorsJohansson H, Sterky F, Amini B, Lundeberg J, Kleczkowski LA
TitleMolecular cloning and characterization of a cDNA encoding poplar UDP-glucose dehydrogenase, a key gene of hemicellulose/pectin formation.
[13]
PubMed ID14686915
JournalEur J Biochem
Year2004
Volume271
Pages14-22
AuthorsGe X, Penney LC, van de Rijn I, Tanner ME
TitleActive site residues and mechanism of UDP-glucose dehydrogenase.
[14]
PubMed ID20863317
JournalBiochem Soc Trans
Year2010
Volume38
Pages1378-85
AuthorsEgger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B
TitleUDP-glucose dehydrogenase: structure and function of a potential drug target.

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.

createdupdated
2004-03-242011-09-14
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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