Structural highlights
Function
GLN1B_MYCTO Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia. Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion. Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis.[UniProtKB:P9WN39]
Publication Abstract from PubMed
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.
Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1: Synthesis, biological evaluation and X-ray crystallographic studies.,Couturier C, Silve S, Morales R, Pessegue B, Llopart S, Nair A, Bauer A, Scheiper B, Poverlein C, Ganzhorn A, Lagrange S, Bacque E Bioorg Med Chem Lett. 2015 Apr 1;25(7):1455-9. doi: 10.1016/j.bmcl.2015.02.035., Epub 2015 Feb 23. PMID:25770781[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. 2015 Apr 1;25(7):1455-9. doi: 10.1016/j.bmcl.2015.02.035., Epub 2015 Feb 23. PMID:25770781 doi:http://dx.doi.org/10.1016/j.bmcl.2015.02.035
