Structural highlights
Publication Abstract from PubMed
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.
Structure of the complex of Neisseria gonorrhoeae N-acetyl-l-glutamate synthase with a bound bisubstrate analog.,Zhao G, Allewell NM, Tuchman M, Shi D Biochem Biophys Res Commun. 2012 Dec 20. pii: S0006-291X(12)02412-6. doi:, 10.1016/j.bbrc.2012.12.064. PMID:23261468[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao G, Allewell NM, Tuchman M, Shi D. Structure of the complex of Neisseria gonorrhoeae N-acetyl-l-glutamate synthase with a bound bisubstrate analog. Biochem Biophys Res Commun. 2012 Dec 20. pii: S0006-291X(12)02412-6. doi:, 10.1016/j.bbrc.2012.12.064. PMID:23261468 doi:http://dx.doi.org/10.1016/j.bbrc.2012.12.064
