3ZXR

Crystal structure of Mycobacterium Tuberculosis Glutamine Synthetase in complex with tri-substituted imidazole inhibitor (3-(2-tert-butyl- 5-(pyridin-4-yl)-1H-imidazol-4-yl)quinoline) and L-methionine-S- sulfoximine phosphate.

Summary for 3ZXR

• Entry DOI: 10.2210/pdb3zxr/pdb
• Related: 1HTO 1HTQ 2BVC 2WGS 2WHI 3ZXV
• Descriptor: GLUTAMINE SYNTHETASE 1, 3-(2-TERT-BUTYL-5-(PYRIDIN-4-YL)-1H-IMIDAZOL-4-YL)QUINOLINE, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: ligase, nucleotide-binding, taut state, rv2220, mt2278, glna1
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 6
• Total formula weight: 332260.10

Authors

Nilsson, M.T.,Mowbray, S.L. (deposition date: 2011-08-15, release date: 2012-04-04, Last modification date: 2023-12-20)

Primary citation

Gising, J.,Nilsson, M.T.,Odell, L.R.,Yahiaoui, S.,Lindh, M.,Iyer, H.,Sinha, A.M.,Srinivasa, B.R.,Larhed, M.,Mowbray, S.L.,Karlen, A.
Trisubstituted Imidazoles as Mycobacterium Tuberculosis Glutamine Synthetase Inhibitors.
J.Med.Chem., 55:2894-, 2012

PubMed Abstract: Mycobacterium tuberculosis glutamine synthetase (MtGS) is a promising target for antituberculosis drug discovery. In a recent high-throughput screening study we identified several classes of MtGS inhibitors targeting the ATP-binding site. We now explore one of these classes, the 2-tert-butyl-4,5-diarylimidazoles, and present the design, synthesis, and X-ray crystallographic studies leading to the identification of MtGS inhibitors with submicromolar IC(50) values and promising antituberculosis MIC values.

PubMed: 22369127
DOI: 10.1021/JM201212H

Experimental method

X-RAY DIFFRACTION (2.15 Å)