4XYC

NANOMOLAR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE 1: SYNTHESIS, BIOLOGICAL EVALUATION AND X-RAY CRYSTALLOGRAPHIC STUDIES

Summary for 4XYC

• Entry DOI: 10.2210/pdb4xyc/pdb
• Descriptor: Glutamine synthetase 1, 9-phenyl-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one (2 entities in total)
• Functional Keywords: ligase, atp binding, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm : P9WN38
• Total number of polymer chains: 24
• Total formula weight: 1294200.89

Authors

Couturier, C.,Silve, S.,Morales, R.,Ppessegue, B.,Llopart, S.,Nair, A.,Bauer, A.,Scheiper, B.,poeverlein, c.,Ganzhorn, A.,Lagrange, S.,Bacque, E. (deposition date: 2015-02-02, release date: 2015-03-25, Last modification date: 2024-01-10)

Primary citation

Couturier, C.,Silve, S.,Morales, R.,Pessegue, B.,Llopart, S.,Nair, A.,Bauer, A.,Scheiper, B.,Poverlein, C.,Ganzhorn, A.,Lagrange, S.,Bacque, E.
Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1: Synthesis, biological evaluation and X-ray crystallographic studies.
Bioorg.Med.Chem.Lett., 25:1455-1459, 2015

PubMed Abstract: A series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit M. tuberculosis glutamine synthetase (GlnA1) has been identified by high throughput screening. Exploration of this series was performed owing to a short chemistry program. Despite possibly nanomolar inhibitions, none of these compounds was active on whole cell Mtb, suggesting that GlnA1 may not be a suitable target to find new anti-tubercular drugs.

PubMed: 25770781
DOI: 10.1016/j.bmcl.2015.02.035

Experimental method

X-RAY DIFFRACTION (3.3 Å)