3ZXV

Crystal structure of Mycobacterium Tuberculosis Glutamine Synthetase in complex with tri-substituted imidazole inhibitor (4-(2-tert-butyl- 4-(6-methoxynaphthalen-2-yl)-1H-imidazol-5-yl)pyridin-2-amine) and L- methionine-S-sulfoximine phosphate

Summary for 3ZXV

• Entry DOI: 10.2210/pdb3zxv/pdb
• Related: 1HTO 1HTQ 2BVC 2WGS 2WHI 3ZXR
• Descriptor: GLUTAMINE SYNTHETASE 1, 4-(2-TERT-BUTYL-4-(6-METHOXYNAPHTHALEN-2-YL)-3H-IMIDAZOL-4-YL)PYRIDIN-2-AMINE, 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: 332524.42

Authors

Nilsson, M.T.,Mowbray, S.L. (deposition date: 2011-08-16, 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 (2.26 Å)