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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1aam

E.C. nameaspartate transaminase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 2.6.1.1
CSA Homologues of 1aamThere are 265 Homologs
CSA Entries With UniProtID P00509
CSA Entries With EC Number 2.6.1.1
PDBe Entry 1aam
PDBSum Entry 1aam
MACiE Entry 1aam

Literature Report

IntroductionAspartyl transferase is able to catalyse the PLP dependent transamination reaction between aspartate and 2-oxoglutarate, forming oxaloacetate and glutamate. It is part of the family of PLP dependent amino acid transferase enzymes which have high sequence homology and identical active site organisation, with the only difference being in the amino acid and ketoacid substrates. The enzymes all play key roles in the catabolism of amino acids as the products feed into the Krebs cycle and the Urea cycle.
MechansimThe reaction follows a ping-pong mechanism. In the first step, the cofactor PLP is transferred from Lys 258 to the aspartate alpha amino group, with the nitrogen atom acting as a nucleophile following deprotonation by Asp 222, and Trp 140 sterically constraining the PLP to allow attack. The aspartate-PLP intermediate then is deprotonated by Lys 258 causing the formation of a ketamine rather than an aldimine. This is then the target for nucleophilic attack by a water molecule, leading to the generation of an amino group bound to the PLP and the release of oxaloacetate. Subsequent reversal of the reaction steps described occurs except with the carboxyl group of the alpha keto glutarate acting as the nucleophile leading to the formation of glutamate and the completion of the reaction cycle.
Reaction

Catalytic Sites for 1aam

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TrpA142130macie:sideChainSterically constrains the PLP cofactor in order to make nucleophilic attack by the aspartate on PLP more favourable.
AspA223211macie:sideChainActs as acid base to facilitate deprotonation of the aspartate's alpha amino group to allow it to act as a nucleophile and attack the PLP.
LysA258246macie:sideChainBinds to PLP cofactor. Also acts as acid base for the conversion of the aldimine to the ketimine forms of the PLP-aspartate intermediate.

Literature References

Notes:
Smith DL
2.8-A-resolution crystal structure of an active-site mutant of aspartate aminotransferase from Escherichia coli.
Biochemistry 1989 28 8161-8167
PubMed: 2513875
Kirsch JF
Mechanism of action of aspartate aminotransferase proposed on the basis of its spatial structure.
J Mol Biol 1984 174 497-525
PubMed: 6143829
Yano T
Role of Asp222 in the catalytic mechanism of Escherichia coli aspartate aminotransferase: the amino acid residue which enhances the function of the enzyme-bound coenzyme pyridoxal 5'-phosphate.
Biochemistry 1992 31 5878-5887
PubMed: 1610831
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