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Structure of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog.

ABSTRACT: N-Acetyl-L-glutamate synthase catalyzes the conversion of AcCoA and glutamate to CoA and N-acetyl-L-glutamate (NAG), the first step of the arginine biosynthetic pathway in lower organisms. In mammals, NAG is an obligate cofactor of carbamoyl phosphate synthetase I in the urea cycle. We have previously reported the structures of NAGS from Neisseria gonorrhoeae (ngNAGS) with various substrates bound. Here we reported the preparation of the bisubstrate analog, CoA-S-acetyl-L-glutamate, the crystal structure of ngNAGS with CoA-NAG bound, and kinetic studies of several active site mutants. The results are consistent with a one-step nucleophilic addition-elimination mechanism with Glu353 as the catalytic base and Ser392 as the catalytic acid. The structure of the ngNAGS-bisubstrate complex together with the previous ngNAGS structures delineates the catalytic reaction path for ngNAGS.

SUBMITTER: Zhao G

PROVIDER: S-EPMC3558559 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Structure of the complex of Neisseria gonorrhoeae N-acetyl-L-glutamate synthase with a bound bisubstrate analog.

Zhao Gengxiang G Allewell Norma M NM Tuchman Mendel M Shi Dashuang D

Biochemical and biophysical research communications 20121220 4

N-Acetyl-L-glutamate synthase catalyzes the conversion of AcCoA and glutamate to CoA and N-acetyl-L-glutamate (NAG), the first step of the arginine biosynthetic pathway in lower organisms. In mammals, NAG is an obligate cofactor of carbamoyl phosphate synthetase I in the urea cycle. We have previously reported the structures of NAGS from Neisseria gonorrhoeae (ngNAGS) with various substrates bound. Here we reported the preparation of the bisubstrate analog, CoA-S-acetyl-L-glutamate, the crystal ...[more]

PMID: 23261468

Similar Datasets

The crystal structure of N-acetyl-L-glutamate synthase from Neisseria gonorrhoeae provides insights into mechanisms of catalysis and regulation.

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Structure of N-acetyl-L-glutamate synthase/kinase from Maricaulis maris with the allosteric inhibitor L-arginine bound.

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