4I49

Structure of ngNAGS bound with bisubstrate analog CoA-NAG

Summary for 4I49

• Entry DOI: 10.2210/pdb4i49/pdb
• Related: 2R2V 3B8G 3D2M 3D2P
• Descriptor: Amino-acid acetyltransferase, (2S)-2-({(3S,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14,20-trioxo-2,4,6-trioxa-18-thia-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaicosan-20-yl}amino)pentanedioic acid (non-preferred name), SULFATE ION, ... (4 entities in total)
• Functional Keywords: protein-bisubstrate analog complex, synthase, transferase
• Biological source: Neisseria gonorrhoeae SK-93-1035
• Total number of polymer chains: 1
• Total formula weight: 50286.24

Authors

Shi, D.,Zhao, G.,Allewell, N.M.,Tuchman, M. (deposition date: 2012-11-27, release date: 2013-01-09, Last modification date: 2023-09-20)

Primary citation

Zhao, G.,Allewell, N.M.,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., 430:1253-1258, 2013

PubMed 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.

PubMed: 23261468
DOI: 10.1016/j.bbrc.2012.12.064

Experimental method

X-RAY DIFFRACTION (2.75 Å)