2bvc: Difference between revisions

Revision as of 17:42, 21 February 2008

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE IN COMPLEX WITH A TRANSITION STATE MIMIC

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 with , , and as ligands. Active as Glutamate--ammonia ligase, with EC number 6.3.1.2 Known structural/functional Site: . 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 Thu Feb 21 16:42:00 2008

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 ==Overview==
-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.
+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 Structure==
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 [[Category: Mycobacterium tuberculosis]]
 [[Category: Single protein]]
-[[Category: Jones, T.A.]]
+[[Category: Jones, T A.]]
-[[Category: Krajewski, W.W.]]
+[[Category: Krajewski, W W.]]
-[[Category: Mowbray, S.L.]]
+[[Category: Mowbray, S L.]]
 [[Category: ADP]]
 [[Category: CL]]
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 [[Category: transition state mimic]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:28:12 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:42:00 2008''