EzCatDB: D00614
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DB codeD00614
CATH domainDomain 13.40.605.10 : Aldehyde Dehydrogenase; Chain A, domain 1
Domain 23.40.309.10 : Aldehyde Dehydrogenase; Chain A, domain 2Catalytic domain
E.C.1.2.1.41

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

Enzyme Name
UniProtKBKEGG

Q9WYC9P54885
Protein nameGamma-glutamyl phosphate reductaseGamma-glutamyl phosphate reductaseGlutamate-5-semialdehyde dehydrogenase
Beta-glutamylphosphate reductase
Gamma-glutamyl phosphate reductase
Beta-Glutamylphosphate reductase
Glutamate semialdehyde dehydrogenase
Glutamate-gamma-semialdehyde dehydrogenase
SynonymsGPR
EC 1.2.1.41
Glutamate-5-semialdehyde dehydrogenase
Glutamyl-gamma-semialdehyde dehydrogenase
GSA dehydrogenase
GPR
EC 1.2.1.41
Glutamate-5-semialdehyde dehydrogenase
GSA dehydrogenase
Glutamyl-gamma-semialdehyde dehydrogenase
RefSeqNP_228105.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
NP_014968.1 (Protein)
NM_001183743.1 (DNA/RNA sequence)
PfamPF00171 (Aldedh)
[Graphical view]
PF00171 (Aldedh)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00330Arginine and proline metabolism

UniProtKB:Accession NumberQ9WYC9P54885
Entry namePROA_THEMAPROA_YEAST
ActivityL-glutamate 5-semialdehyde + phosphate + NADP(+) = L-glutamyl 5-phosphate + NADPH.L-glutamate 5-semialdehyde + phosphate + NADP+ = L-glutamyl 5-phosphate + NADPH.
Subunit

Subcellular locationCytoplasm (By similarity).
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC01165C00009C00006C03287C00005C00080I00158I00159I00160
CompoundL-glutamate 5-semialdehydephosphateNADP+L-glutamyl 5-phosphateNADPHH+Peptidyl-Cys-hydroxyl-L-glutamatePeptidyl-Cys-acyl intermediate (with L-glutamate)Peptidyl-Cys-tetrahedral intermediate (with L-glutamyl-phosphate)
Typeamino acids,carbohydratephosphate group/phosphate ionamide group,amine group,nucleotideamino acids,carbohydrate,phosphate group/phosphate ionamide group,amine group,nucleotideothers


ChEBI17232
58066
26078
18009
17798
16474
15378



PubChem49791979
193305
22486802
1004
5886
193475
5884
1038



                 
1o20A01UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vluA01UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vluB01UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1o20A02UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vluA02UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1vluB02UnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound

Active-site residues
resource
literature[2] and information on homologous enzymes
pdbCatalytic residuescomment
          
1o20A01ARG 124;ARG 202
 
1vluA01ARG 125;ARG 205
 
1vluB01ARG 125;ARG 205
 
1o20A02CYS 255;ASN 256;HIS 338
 
1vluA02CYS 258;ASN 259;HIS 356
invisible 254-257
1vluB02       ;ASN 259;HIS 256
invisible 254-258

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.1, p.158-159

references
[1]
PubMed ID10210192
JournalProtein Sci
Year1999
Volume8
Pages137-46
AuthorsPerozich J, Nicholas H, Wang BC, Lindahl R, Hempel J
TitleRelationships within the aldehyde dehydrogenase extended family.
[2]
PubMed ID14705032
JournalProteins
Year2004
Volume54
Pages157-61
AuthorsPage 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
TitleCrystal structure of gamma-glutamyl phosphate reductase (TM0293) from Thermotoga maritima at 2.0 A resolution.
Related PDB1o20

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.

createdupdated
2012-09-262012-10-19


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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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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