2bvc
CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE IN COMPLEX WITH A TRANSITION STATE MIMIC
| |||||||
| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , and | ||||||
| Activity: | Glutamate--ammonia ligase, with EC number 6.3.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
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 an active enzyme, mimics the phosphorylated tetrahedral adduct at the transition state. Some differences in ligand interactions of the protein with both phosphorylated compound and nucleotide are observed compared with earlier structures; a third metal ion also is found. The importance of these differences in the catalytic mechanism is discussed; the results will help guide the search for specific inhibitors of potential therapeutic interest.
About this StructureAbout this Structure
2BVC is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
ReferenceReference
Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights., Krajewski WW, Jones TA, Mowbray SL, Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10499-504. Epub 2005 Jul 18. PMID:16027359
Page seeded by OCA on Sun Mar 23 14:48:16 2008