DB code: D00614

CATH domain 3.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1
3.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2 Catalytic domain
E.C. 1.2.1.41
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2 D00020 D00021 D00022 D00475
3.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1 D00020 D00021 D00022 D00475

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9WYC9 Gamma-glutamyl phosphate reductase
GPR
EC 1.2.1.41
Glutamate-5-semialdehyde dehydrogenase
Glutamyl-gamma-semialdehyde dehydrogenase
GSA dehydrogenase
NP_228105.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PF00171 (Aldedh)
[Graphical View]
P54885 Gamma-glutamyl phosphate reductase
GPR
EC 1.2.1.41
Glutamate-5-semialdehyde dehydrogenase
GSA dehydrogenase
Glutamyl-gamma-semialdehyde dehydrogenase
NP_014968.1 (Protein)
NM_001183743.1 (DNA/RNA sequence)
PF00171 (Aldedh)
[Graphical View]

KEGG enzyme name
Glutamate-5-semialdehyde dehydrogenase
Beta-glutamylphosphate reductase
Gamma-glutamyl phosphate reductase
Beta-Glutamylphosphate reductase
Glutamate semialdehyde dehydrogenase
Glutamate-gamma-semialdehyde dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9WYC9 PROA_THEMA L-glutamate 5-semialdehyde + phosphate + NADP(+) = L-glutamyl 5-phosphate + NADPH. Cytoplasm (By similarity).
P54885 PROA_YEAST L-glutamate 5-semialdehyde + phosphate + NADP+ = L-glutamyl 5-phosphate + NADPH.

KEGG Pathways
Map code Pathways E.C.
MAP00330 Arginine and proline metabolism

Compound table
Substrates Products Intermediates
KEGG-id C01165 C00009 C00006 C03287 C00005 C00080 I00158 I00159 I00160
E.C.
Compound L-glutamate 5-semialdehyde phosphate NADP+ L-glutamyl 5-phosphate NADPH H+ Peptidyl-Cys-hydroxyl-L-glutamate Peptidyl-Cys-acyl intermediate (with L-glutamate) Peptidyl-Cys-tetrahedral intermediate (with L-glutamyl-phosphate)
Type amino acids,carbohydrate phosphate group/phosphate ion amide group,amine group,nucleotide amino acids,carbohydrate,phosphate group/phosphate ion amide group,amine group,nucleotide others
ChEBI 17232
58066
26078
18009
17798
16474
15378
PubChem 193305
49791979
1004
22486802
5886
193475
5884
1038
1o20A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vluA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vluB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1o20A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vluA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1vluB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[2] and information on homologous enzymes

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1o20A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 124;ARG 202
1vluA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 125;ARG 205
1vluB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 125;ARG 205
1o20A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 255;ASN 256;HIS 338
1vluA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 258;ASN 259;HIS 356 invisible 254-257
1vluB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASN 259;HIS 256 invisible 254-258

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.1, p.158-159

References
[1]
Resource
Comments
Medline ID
PubMed ID 10210192
Journal Protein Sci
Year 1999
Volume 8
Pages 137-46
Authors Perozich J, Nicholas H, Wang BC, Lindahl R, Hempel J
Title Relationships within the aldehyde dehydrogenase extended family.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 14705032
Journal Proteins
Year 2004
Volume 54
Pages 157-61
Authors Page R, Nelson MS, von Delft F, Elsliger MA, Canaves JM, Brinen LS, Dai X, Deacon AM, Floyd R, Godzik A, Grittini C, Grzechnik SK, Jaroszewski L, Klock HE, Koesema E, Kovarik JS, Kreusch A, Kuhn P, Lesley SA, McMullan D, McPhillips TM, Miller MD, Morse A, Moy K, Ouyang J, Robb A, Rodrigues K, Schwarzenbacher R, Spraggon G, Stevens RC, van den Bedem H, Velasquez J, Vincent J, Wang X, West B, Wolf G, Hodgson KO, Wooley J, Wilson IA
Title Crystal structure of gamma-glutamyl phosphate reductase (TM0293) from Thermotoga maritima at 2.0 A resolution.
Related PDB 1o20
Related UniProtKB

Comments
This enzyme is homologous to aldehyde dehydrogenases (D00020, D00021, D00022 and D00475 in EzCatDB).
All these homologous enzymes share a catalytic cysteine residue, although other catalytic residues are not so conserved. The catalytic cysteine acts as a nucleophile, which is attached to carbonyl carbon to form an alcohol intermediate (I00156). The alcohol intermediate is oxidized by NAD(P)+ to form acyl intermediate (I00154).
In contrast to those aldehyde dehydrogenases, whose acyl intermediate can by hydrolyzed to release a product carboxylate, this enzyme must catalyze phoshporolysis reaction of the acyl intermediate, releasing a phosphorylated carboxylate product.
Thus, although the catalytic mechanism has not been elucidated yet, this enzyme may catalyze the following reactions:
(A) Addition of catalytic cysteine to carbonyl carbon of substrate aldehyde, forming an alcohol intermediate (I00158):
(B) Hydride transfer from an alcohol intermediate to nicotinamide of NADP+, forming an acyl intermediate (I00159):
(B0) Alghough more information is necessary, His338 (of 1o20) may act as a general base to deprotonate the hydroxyl group, whereas Asn256 might stabilize the oxygen atom.
(C) Phosphorolysis of acyl intermediate:
(C0) Arg124 and Arg202 (of 1o20) may stabilize the phosphorous during the reaction. During the reaction, tetrahedral phosphorylated intermediate (I00160) can be formed.

Created Updated
2012-09-26 2012-10-19