EzCatDB: D00279

DB codeD00279
CATH domainDomain 13.90.1150.10
Domain 23.40.640.10Catalytic domain
E.C.5.4.3.8
CSA2gsa
MACiEM0195

CATH domainRelated DB codes (homologues)
3.40.640.10D00085,D00092,D00101,D00102,D00103,D00104,D00107,D00108,D00109,D00255,D00257,D00258,D00265,D00269,D00515,M00031
3.90.1150.10D00085,D00092,D00101,D00102,D00103,D00104,D00107,D00108,D00109,D00255,D00257,D00258,D00265,D00269,D00515,M00031

Enzyme Name
Swiss-protKEGG

P24630
Protein nameGlutamate-1-semialdehyde 2,1-aminomutaseglutamate-1-semialdehyde 2,1-aminomutase
glutamate-1-semialdehyde aminotransferase
SynonymsGSA
EC 5.4.3.8
Glutamate-1-semialdehyde aminotransferase
GSA-AT

KEGG pathways
MAP codePathways
MAP00860Porphyrin and chlorophyll metabolism

Swiss-prot:Accession NumberP24630
Entry nameGSA_SYNP6
Activity(S)-4-amino-5-oxopentanoate = 5- aminolevulinate.
SubunitHomodimer.
Subcellular locationCytoplasm (Potential).
CofactorPyridoxal phosphate.


CofactorsSubstratesProductsintermediates
KEGG-idC00647C03741C00430


C00018I00003


CompoundPyridoxamine 5'-phosphate(S)-4-Amino-5-oxopentanoate5-AminolevulinateKetimine intermediate-1 Quinonoid intermediate-1 External aldimine intermediate-1 Internal aldimine intermediate (PLP)4,5-diaminovalerate (DAV)External aldimine intermediate-2 Quinonoid intermediate-2 Ketimine intermediate-2
Typeamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ionamino acids,carbohydrateamino acids,carbohydrate







2gsaA01UnboundUnboundUnbound


UnboundUnbound


2gsaB01UnboundUnboundUnbound


UnboundUnbound


3gsaA01UnboundUnboundUnbound


UnboundUnbound


3gsaB01UnboundUnboundUnbound


UnboundUnbound


3gsbA01UnboundUnboundUnbound


UnboundUnbound


3gsbB01UnboundUnboundUnbound


UnboundUnbound


4gsaA01UnboundUnboundUnbound


UnboundUnbound


4gsaB01UnboundUnboundUnbound


UnboundUnbound


2gsaA02Bound:PMPUnboundUnbound


UnboundUnbound


2gsaB02Analogue:PLPUnboundUnbound


Intermediate-bound:PLPUnbound


3gsaA02Analogue:PLPUnboundUnbound


Intermediate-bound:PLPIntermediate-analogue:GAB


3gsaB02Analogue:PLPUnboundUnbound


UnboundUnbound


3gsbA02Bound:PMPAnalogue:GABUnbound


UnboundUnbound


3gsbB02Bound:PMPUnboundUnbound


UnboundUnbound


4gsaA02Analogue:PLPUnboundUnbound


Intermediate-bound:PLPUnbound


4gsaB02Analogue:PLPUnboundUnbound


Intermediate-bound:PLPUnbound



Active-site residues
resource
Swiss-prot;P24630 & literature [7], [13]
pdbCatalytic residuesCofactor-binding residues
2gsaA01

2gsaB01

3gsaA01

3gsaB01

3gsbA01

3gsbB01

4gsaA01

4gsaB01

2gsaA02ASP 245;LYS 273
LYS 273(PLP binding)
2gsaB02ASP 245;LYS 273
LYS 273(PLP binding)
3gsaA02ASP 245;LYS 273
LYS 273(PLP binding)
3gsaB02ASP 245;LYS 273
LYS 273(PLP binding)
3gsbA02ASP 245;LYS 273
LYS 273(PLP binding)
3gsbB02ASP 245;LYS 273
LYS 273(PLP binding)
4gsaA02ASP 245;LYS 273
LYS 273(PLP binding)
4gsaB02ASP 245;LYS 273
LYS 273(PLP binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Scheme I
[3]Scheme 2, p.1588
[4]Scheme 1
[6]Fig.5
[7]Fig.1, p.4870-4871
[8]Scheme 1
[11]FIG.1

references
[1]
PubMed ID1643048
JournalBiochemistry
Year1992
Volume31
Pages7143-51
AuthorsIlag LL, Jahn D
TitleActivity and spectroscopic properties of the Escherichia coli glutamate 1-semialdehyde aminotransferase and the putative active site mutant K265R.
[2]
PubMed ID1445864
JournalBiochemistry
Year1992
Volume31
Pages11249-54
AuthorsSmith MA, Kannangara CG, Grimm B
TitleGlutamate 1-semialdehyde aminotransferase: anomalous enantiomeric reaction and enzyme mechanism.
[3]
PubMed ID1730703
JournalJ Biol Chem
Year1992
Volume267
Pages1584-8
AuthorsPugh CE, Harwood JL, John RA
TitleMechanism of glutamate semialdehyde aminotransferase. Roles of diamino- and dioxo-intermediates in the synthesis of aminolevulinate.
[4]
PubMed ID8352736
JournalBiochem J
Year1993
Volume293
Pages697-701
AuthorsTyacke RJ, Harwood JL, John RA
TitleProperties of the pyridoxaldimine form of glutamate semialdehyde aminotransferase (glutamate-1-semialdehyde 2,1-aminomutase) and analysis of its role as an intermediate in the formation of aminolaevulinate.
[5]
PubMed ID7932714
JournalJ Mol Biol
Year1994
Volume242
Pages591-4
AuthorsHennig M, Grimm B, Jenny M, Muller R, Jansonius JN
TitleCrystallization and preliminary X-ray analysis of wild-type and K272A mutant glutamate 1-semialdehyde aminotransferase from Synechococcus.
[6]
PubMed ID8519748
JournalBiochemistry
Year1995
Volume34
Pages15918-24
AuthorsBrody S, Andersen JS, Kannangara CG, Meldgaard M, Roepstorff P, von Wettstein D
TitleCharacterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID97289685
PubMed ID9144156
JournalProc Natl Acad Sci U S A
Year1997
Volume94
Pages4866-71
AuthorsHennig M, Grimm B, Contestabile R, John RA, Jansonius JN
TitleCrystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity.
Related PDB2gsa,3gsa,3gsa,4gsa
Related Swiss-protP24630
[8]
PubMed ID10660540
JournalJ Biol Chem
Year2000
Volume275
Pages3879-86
AuthorsContestabile R, Angelaccio S, Maytum R, Bossa F, John RA
TitleThe contribution of a conformationally mobile, active site loop to the reaction catalyzed by glutamate semialdehyde aminomutase.
[9]
PubMed ID11726494
JournalEMBO J
Year2001
Volume20
Pages6583-90
AuthorsMoser J, Schubert WD, Beier V, Bringemeier I, Jahn D, Heinz DW
TitleV-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis.
[10]
PubMed ID12459457
JournalFEBS Lett
Year2002
Volume532
Pages27-30
AuthorsMeskauskiene R, Apel K
TitleInteraction of FLU, a negative regulator of tetrapyrrole biosynthesis, with the glutamyl-tRNA reductase requires the tetratricopeptide repeat domain of FLU.
[11]
PubMed ID12878592
JournalJ Biol Chem
Year2003
Volume278
Pages40521-6
AuthorsD'Aguanno S, Gonzales IN, Simmaco M, Contestabile R, John RA
TitleStereochemistry of the reactions of glutamate-1-semialdehyde aminomutase with 4,5-diaminovalerate.
[12]
PubMed ID15498941
JournalProtein Sci
Year2004
Volume13
Pages2992-3005
AuthorsPaiardini A, Bossa F, Pascarella S
TitleEvolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
[13]
PubMed ID16564539
JournalJ Mol Biol
Year2006
Volume[Epub ahead of print]
Pages[Epub ahead of print]
AuthorsSchulze JO, Schubert WD, Moser J, Jahn D, Heinz DW
TitleEvolutionary Relationship between Initial Enzymes of Tetrapyrrole Biosynthesis.

comments
Since the reaction starts and ends with the cofactor in the pyridoxamine phosphate form (PMP), PMP (C00647) is annotated as cofactor in this entry.
This enzyme catalyzes intramolecular transamination, which is similar to other transaminases (E.C. 2.6.1.-), such as aspartate aminotransferase (D00101 in EzCatDB), except that the reaction starts and ends with the cofactor in the PMP form, instead of PLP form.
(A) Schiff-base formation of PMP with carbonyl group of the substrate, (S)-4-Amino-5-oxopentanoate (GSA), leading to a ketimine intermediate:
(B) Isomerization (change in the position of double-bond), leading to external aldimine (PLP-GSA):
(C) Formation of internal aldimine, leading to the elimination of an intermediate, 4,5-diamiovalerate (DAV), from PLP:
(D) Formation of external aldimine (with another amine group of DAV):
(B) Isomerization (change in the position of double-bond), leading to a ketimine intermediate:
(C) Schiff-base deformation, releasing the product, 5-Aminolevulinate, and PMP:

createdupdated
2004-04-052009-02-26
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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