DB code: D00835

CATH domain 3.40.50.1970 : Rossmann fold
1.20.1090.10 : Dehydroquinate synthase-like, alpha domain Catalytic domain
E.C. 1.1.1.6
CSA
M-CSA
MACiE M0312

CATH domain Related DB codes (homologues)
1.20.1090.10 : Dehydroquinate synthase-like, alpha domain D00840
3.40.50.1970 : Rossmann fold D00840

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P32816 Glycerol dehydrogenase
GlyDH
GLDH
GDH
EC 1.1.1.6
PF00465 (Fe-ADH)
[Graphical View]
Q97IL4
Glycerol dehydrogenase
[Graphical View] NP_348253.1 (Protein)
NC_003030.1 (DNA/RNA sequence)
Q9WYQ4 Glycerol dehydrogenase
GLDH
GDH
EC 1.1.1.6
PF00465 (Fe-ADH)
[Graphical View] 		NP_228233.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
O13702 Glycerol dehydrogenase
GLDH
GDH
EC 1.1.1.6
PF00465 (Fe-ADH)
[Graphical View] 		NP_593651.1 (Protein)
NM_001019083.2 (DNA/RNA sequence)

KEGG enzyme name
Glycerol dehydrogenase
Glycerin dehydrogenase
NAD+-linked glycerol dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P32816 GLDA_BACST Glycerol + NAD+ = glycerone + NADH. Homooctamer. Binds 1 zinc ion per subunit.
Q97IL4 Q97IL4_CLOAB
Q9WYQ4 GLDA_THEMA Glycerol + NAD+ = glycerone + NADH. Binds 1 zinc ion per subunit (By similarity).
O13702 GLD1_SCHPO Glycerol + NAD+ = glycerone + NADH. Mitochondrion Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00561 Glycerolipid metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00116 C00003 C00184 C00004 C00080
E.C.
Compound Zinc glycerol NAD+ glycerone NADH H+
Type heavy metal carbohydrate amide group,amine group,nucleotide carbohydrate amide group,amine group,nucleotide others
ChEBI 29105
 29105
 		17754
 17754
 		15846
 15846
 		16016
 16016
 		16908
 16908
 		15378
 15378
PubChem 32051
 32051
 		753
 753
 		5893
 5893
 		670
 670
 		439153
 439153
 		1038
 1038
1jpuA01 Unbound Unbound Unbound Unbound Unbound
1jq5A01 Unbound Unbound Bound:NAD Unbound Unbound
1jqaA01 Unbound Unbound Unbound Unbound Unbound
3ce9A01 Unbound Unbound Unbound Unbound Unbound
3ce9B01 Unbound Unbound Unbound Unbound Unbound
3ce9C01 Unbound Unbound Unbound Unbound Unbound
3ce9D01 Unbound Unbound Unbound Unbound Unbound
1ta9A01 Unbound Unbound Unbound Unbound Unbound
1ta9B01 Unbound Unbound Unbound Unbound Unbound
1kq3A01 Unbound Unbound Unbound Unbound Unbound
1jpuA02 Bound:2x_ZN Unbound Unbound Unbound Unbound
1jq5A02 Bound:2x_ZN Unbound Unbound Unbound Unbound
1jqaA02 Unbound Bound:GOL Unbound Unbound Unbound
3ce9A02 Bound:2x_ZN Unbound Unbound Unbound Unbound
3ce9B02 Bound:2x_ZN Unbound Unbound Unbound Unbound
3ce9C02 Bound:2x_ZN Unbound Unbound Unbound Unbound
3ce9D02 Bound:2x_ZN Unbound Unbound Unbound Unbound
1ta9A02 Bound:_Zn,Analogue;__K Bound:GOL_1401 Unbound Unbound Unbound
1ta9B02 Bound:_Zn,Analogue;__K Bound:GOL_1402 Unbound Unbound Unbound
1kq3A02 Bound:_Zn,Analogue;_CL Analogue:TRS Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3], [5], [6], [7], [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1jpuA01
1jq5A01
1jqaA01
3ce9A01
3ce9B01
3ce9C01
3ce9D01
1ta9A01
1ta9B01
1kq3A01
1jpuA02 HIS 259 ASP 173;HIS 256;HIS 274(Catalytic zinc binding) mutant S305C
1jq5A02 HIS 259 ASP 173;HIS 256;HIS 274(Catalytic zinc binding) mutant S305C
1jqaA02 HIS 259 ASP 173;HIS 256;HIS 274(Catalytic zinc binding) mutant S305C
3ce9A02 HIS 254 ASP 171;HIS 250;HIS 266(Catalytic zinc binding)
3ce9B02 HIS 254 ASP 171;HIS 250;HIS 266(Catalytic zinc binding)
3ce9C02 HIS 254 ASP 171;HIS 250;HIS 266(Catalytic zinc binding)
3ce9D02 HIS 254 ASP 171;HIS 250;HIS 266(Catalytic zinc binding)
1ta9A02 HIS 318 ASP 232;HIS 315;HIS 333(Catalytic zinc binding)
1ta9B02 HIS 318 ASP 232;HIS 315;HIS 333(Catalytic zinc binding)
1kq3A02 HIS 255 ASP 169;HIS 252;HIS 269(Catalytic zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.790, p.795-796
[5]
Fig.6, p.847
[6]
p.371
[7]
Fig.6, p.1080-1081
[9]
p.3964-3966

References
[1]
Resource
Comments
Medline ID
PubMed ID 8185833
Journal Crit Rev Microbiol
Year 1994
Volume 20
Pages 13-56
Authors Reid MF, Fewson CA
Title Molecular characterization of microbial alcohol dehydrogenases.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-393 IN COMPLEX WITH NAD; ZINC AND SUBSTRATE ANALOG, SUBUNIT. F29
Medline ID
PubMed ID 9685163
Journal Nature
Year 1998
Volume 394
Pages 299-302
Authors Carpenter EP, Hawkins AR, Frost JW, Brown KA
Title Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis.
Related PDB 1dqs
Related UniProtKB P07547
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF MUTANT CYS-305 IN COMPLEXES WITH ZINC; NAD AND SUBSTRATE, DOMAIN, COFACTOR, SUBUNIT, MUTAGENESIS OF SER-305.
Medline ID
PubMed ID 11566129
Journal Structure
Year 2001
Volume 9
Pages 789-802
Authors Ruzheinikov SN, Burke J, Sedelnikova S, Baker PJ, Taylor R, Bullough PA, Muir NM, Gore MG, Rice DW
Title Glycerol dehydrogenase. structure, specificity, and mechanism of a family III polyol dehydrogenase.
Related PDB 1jpu 1jq5 1jqa
Related UniProtKB P32816
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH ZINC AND SUBSTRATE ANALOG.
Medline ID
PubMed ID 12193646
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 11664-9
Authors Lesley SA, Kuhn P, Godzik A, Deacon AM, Mathews I, Kreusch A, Spraggon G, Klock HE, McMullan D, Shin T, Vincent J, Robb A, Brinen LS, Miller MD, McPhillips TM, Miller MA, Scheibe D, Canaves JM, Guda C, Jaroszewski L, Selby TL, Elsliger MA, Wooley J, Taylor SS, Hodgson KO, Wilson IA, Schultz PG, Stevens RC
Title Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline.
Related PDB 1kq3
Related UniProtKB Q9WYQ4
[5]
Resource
Comments
Medline ID
PubMed ID 12909013
Journal J Mol Biol
Year 2003
Volume 331
Pages 829-60
Authors Bartlett GJ, Borkakoti N, Thornton JM
Title Catalysing new reactions during evolution: economy of residues and mechanism.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12486729
Journal Proteins
Year 2003
Volume 50
Pages 371-4
Authors Brinen LS, Canaves JM, Dai X, Deacon AM, Elsliger MA, Eshaghi S, Floyd R, Godzik A, Grittini C, Grzechnik SK, Guda C, Jaroszewski L, Karlak C, Klock HE, Koesema E, Kovarik JS, Kreusch A, Kuhn P, Lesley SA, McMullan D, McPhillips TM, Miller MA, Miller MD, Morse A, Moy K, Ouyang J, Robb A, Rodrigues K, Selby TL, Spraggon G, Stevens RC, van den Bedem H, Velasquez J, Vincent J, Wang X, West B, Wolf G, Taylor SS, Hodgson KO, Wooley J, Wilson IA
Title Crystal structure of a zinc-containing glycerol dehydrogenase (TM0423) from Thermotoga maritima at 1.5 A resolution.
Related PDB 1kq3
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID
PubMed ID 12962626
Journal Structure
Year 2003
Volume 11
Pages 1071-85
Authors Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL
Title X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.
Related PDB 1pl6 1pl7 1pl8
Related UniProtKB Q00796
[8]
Resource
Comments
Medline ID
PubMed ID 15995211
Journal J Bacteriol
Year 2005
Volume 187
Pages 4957-66
Authors Montella C, Bellsolell L, Perez-Luque R, Badia J, Baldoma L, Coll M, Aguilar J
Title Crystal structure of an iron-dependent group III dehydrogenase that interconverts L-lactaldehyde and L-1,2-propanediol in Escherichia coli.
Related PDB 2bi4 2bl4
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 19011745
Journal Cell Mol Life Sci
Year 2008
Volume 65
Pages 3961-70
Authors Auld DS, Bergman T
Title Medium- and short-chain dehydrogenase/reductase gene and protein families : The role of zinc for alcohol dehydrogenase structure and function.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the group III "iron-activated" alcohol dehydrogenases (literature [1] & [3]).
This enzyme is homologous to dehydroquinate synthase (EC=1.1.1.25; PDB 1dqs).
According to the literature [2] and [3], the hydride transfer reacion by this enzyme proceeds as follows:
(0) Zinc ion, which is bound to Asp173, His256 and His274 (PDB;1jpu) and interacts with two hydroxyl oxygens of substrate, glycerol, may lower the pKa of the C2 hydroxyl oxygen, facilitating its deprotonation.
(1) His259 might act as a general base to deprotonate the C2 hydroxyl oxygen, through a water molecule by proton shuttle, leading to an alkoxide transition-state.
(2) Hydride transfer from the C2 carbon atom to the C4 of the nicotinamide group in the NAD molecule occurs.

Created Updated
2010-02-04 2010-09-01