Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights.

ABSTRACT: Glutamine synthetase catalyzes the ligation of glutamate and ammonia to form glutamine, with the resulting hydrolysis of ATP. The enzyme is a central component of bacterial nitrogen metabolism and is a potential drug target. Here, we report a high-yield recombinant expression system for glutamine synthetase of Mycobacterium tuberculosis together with a simple purification. The procedure allowed the structure of a complex with a phosphorylated form of the inhibitor methionine sulfoximine, magnesium, and ADP to be solved by molecular replacement and refined at 2.1-A resolution. To our knowledge, this study provides the first reported structure for a taut form of the M. tuberculosis enzyme, similar to that observed for the Salmonella enzyme earlier. The phospho compound, generated in situ by

SUBMITTER: Krajewski WW 

PROVIDER: S-EPMC1180770 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature