DB code: D00279

CATH domain	3.90.1150.10 : Aspartate Aminotransferase, domain 1
CATH domain	3.40.640.10 : Aspartate Aminotransferase; domain 2	Catalytic domain
E.C.	5.4.3.8
CSA	2gsa
M-CSA	2gsa
MACiE	M0195

CATH domain	Related DB codes (homologues)
3.40.640.10 : Aspartate Aminotransferase; domain 2	D00085 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00258 D00265 D00269 D00515 M00031
3.90.1150.10 : Aspartate Aminotransferase, domain 1	D00085 D00092 D00101 D00102 D00103 D00104 D00107 D00108 D00109 D00255 D00257 D00258 D00265 D00269 D00515 M00031

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
P24630	Glutamate-1-semialdehyde 2,1-aminomutase	GSA EC 5.4.3.8 Glutamate-1-semialdehyde aminotransferase GSA-AT	YP_171591.2 (Protein) NC_006576.1 (DNA/RNA sequence)	PF00202 (Aminotran_3) [Graphical View]

KEGG enzyme name
glutamate-1-semialdehyde 2,1-aminomutase glutamate-1-semialdehyde aminotransferase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P24630	GSA_SYNP6	(S)-4-amino-5-oxopentanoate = 5- aminolevulinate.	Homodimer.	Cytoplasm (Potential).	Pyridoxal phosphate.

KEGG Pathways
Map code	Pathways	E.C.
MAP00860	Porphyrin and chlorophyll metabolism

Compound table
	Cofactors	Substrates	Products	Intermediates
KEGG-id	C00647	C03741	C00430				C00018	I00003
E.C.				(initial stage:PMP-GSA)	(PMP-GSA)	(PLP-GSA)			(PLP-DAV)	(PMP-DAV)	(final stage:PMP-DAV)
Compound	Pyridoxamine 5'-phosphate	(S)-4-Amino-5-oxopentanoate	5-Aminolevulinate	Ketimine 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
Type	amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion	amino acids,carbohydrate	amino acids,carbohydrate
ChEBI	18335 18335	15757 57501 15757 57501	17549 356416 17549 356416
PubChem	1053 1053	129297 25244684 129297 25244684	137 7048523 137 7048523

2gsaA01	Unbound	Unbound	Unbound				Unbound	Unbound
2gsaB01	Unbound	Unbound	Unbound				Unbound	Unbound
3gsaA01	Unbound	Unbound	Unbound				Unbound	Unbound
3gsaB01	Unbound	Unbound	Unbound				Unbound	Unbound
3gsbA01	Unbound	Unbound	Unbound				Unbound	Unbound
3gsbB01	Unbound	Unbound	Unbound				Unbound	Unbound
4gsaA01	Unbound	Unbound	Unbound				Unbound	Unbound
4gsaB01	Unbound	Unbound	Unbound				Unbound	Unbound
2gsaA02	Bound:PMP	Unbound	Unbound				Unbound	Unbound
2gsaB02	Analogue:PLP	Unbound	Unbound				Intermediate-bound:PLP	Unbound
3gsaA02	Analogue:PLP	Unbound	Unbound				Intermediate-bound:PLP	Intermediate-analogue:GAB
3gsaB02	Analogue:PLP	Unbound	Unbound				Unbound	Unbound
3gsbA02	Bound:PMP	Analogue:GAB	Unbound				Unbound	Unbound
3gsbB02	Bound:PMP	Unbound	Unbound				Unbound	Unbound
4gsaA02	Analogue:PLP	Unbound	Unbound				Intermediate-bound:PLP	Unbound
4gsaB02	Analogue:PLP	Unbound	Unbound				Intermediate-bound:PLP	Unbound

Reference for Active-site residues
resource	references	E.C.
Swiss-prot;P24630 & literature [7], [13]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

2gsaA01
2gsaB01
3gsaA01
3gsaB01
3gsbA01
3gsbB01
4gsaA01
4gsaB01
2gsaA02	ASP 245;LYS 273	LYS 273(PLP binding)
2gsaB02	ASP 245;LYS 273	LYS 273(PLP binding)
3gsaA02	ASP 245;LYS 273	LYS 273(PLP binding)
3gsaB02	ASP 245;LYS 273	LYS 273(PLP binding)
3gsbA02	ASP 245;LYS 273	LYS 273(PLP binding)
3gsbB02	ASP 245;LYS 273	LYS 273(PLP binding)
4gsaA02	ASP 245;LYS 273	LYS 273(PLP binding)
4gsaB02	ASP 245;LYS 273	LYS 273(PLP binding)

References for Catalytic Mechanism
References	Sections	No. 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]
Resource
Comments
Medline ID
PubMed ID	1643048
Journal	Biochemistry
Year	1992
Volume	31
Pages	7143-51
Authors	Ilag LL, Jahn D
Title	Activity and spectroscopic properties of the Escherichia coli glutamate 1-semialdehyde aminotransferase and the putative active site mutant K265R.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	1445864
Journal	Biochemistry
Year	1992
Volume	31
Pages	11249-54
Authors	Smith MA, Kannangara CG, Grimm B
Title	Glutamate 1-semialdehyde aminotransferase: anomalous enantiomeric reaction and enzyme mechanism.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	1730703
Journal	J Biol Chem
Year	1992
Volume	267
Pages	1584-8
Authors	Pugh CE, Harwood JL, John RA
Title	Mechanism of glutamate semialdehyde aminotransferase. Roles of diamino- and dioxo-intermediates in the synthesis of aminolevulinate.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	8352736
Journal	Biochem J
Year	1993
Volume	293
Pages	697-701
Authors	Tyacke RJ, Harwood JL, John RA
Title	Properties 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.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	7932714
Journal	J Mol Biol
Year	1994
Volume	242
Pages	591-4
Authors	Hennig M, Grimm B, Jenny M, Muller R, Jansonius JN
Title	Crystallization and preliminary X-ray analysis of wild-type and K272A mutant glutamate 1-semialdehyde aminotransferase from Synechococcus.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	8519748
Journal	Biochemistry
Year	1995
Volume	34
Pages	15918-24
Authors	Brody S, Andersen JS, Kannangara CG, Meldgaard M, Roepstorff P, von Wettstein D
Title	Characterization of the different spectral forms of glutamate 1-semialdehyde aminotransferase by mass spectrometry.
Related PDB
Related UniProtKB
[7]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
Medline ID	97289685
PubMed ID	9144156
Journal	Proc Natl Acad Sci U S A
Year	1997
Volume	94
Pages	4866-71
Authors	Hennig M, Grimm B, Contestabile R, John RA, Jansonius JN
Title	Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity.
Related PDB	2gsa 3gsa 3gsa 4gsa
Related UniProtKB	P24630
[8]
Resource
Comments
Medline ID
PubMed ID	10660540
Journal	J Biol Chem
Year	2000
Volume	275
Pages	3879-86
Authors	Contestabile R, Angelaccio S, Maytum R, Bossa F, John RA
Title	The contribution of a conformationally mobile, active site loop to the reaction catalyzed by glutamate semialdehyde aminomutase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	11726494
Journal	EMBO J
Year	2001
Volume	20
Pages	6583-90
Authors	Moser J, Schubert WD, Beier V, Bringemeier I, Jahn D, Heinz DW
Title	V-shaped structure of glutamyl-tRNA reductase, the first enzyme of tRNA-dependent tetrapyrrole biosynthesis.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	12459457
Journal	FEBS Lett
Year	2002
Volume	532
Pages	27-30
Authors	Meskauskiene R, Apel K
Title	Interaction of FLU, a negative regulator of tetrapyrrole biosynthesis, with the glutamyl-tRNA reductase requires the tetratricopeptide repeat domain of FLU.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	12878592
Journal	J Biol Chem
Year	2003
Volume	278
Pages	40521-6
Authors	D'Aguanno S, Gonzales IN, Simmaco M, Contestabile R, John RA
Title	Stereochemistry of the reactions of glutamate-1-semialdehyde aminomutase with 4,5-diaminovalerate.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	15498941
Journal	Protein Sci
Year	2004
Volume	13
Pages	2992-3005
Authors	Paiardini A, Bossa F, Pascarella S
Title	Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	16564539
Journal	J Mol Biol
Year	2006
Volume	[Epub ahead of print]
Pages	[Epub ahead of print]
Authors	Schulze JO, Schubert WD, Moser J, Jahn D, Heinz DW
Title	Evolutionary Relationship between Initial Enzymes of Tetrapyrrole Biosynthesis.
Related PDB
Related UniProtKB

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:

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:

Created	Updated
2004-04-05	2009-02-26