Structural highlights
Function
[RELA_MYCTU] In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes both the formation of pppGpp, which is then hydrolyzed to form ppGpp, as well as the hydrolysis of ppGpp. RelA is probably a key factor in the pathogenesis of M.tuberculosis as it regulates the intracellular concentrations of (p)ppGpp.[1] [2]
Publication Abstract from PubMed
Modulation of intracellular guanosine 3',5'-bispyrophosphate ((p)ppGpp) level, the effector of the stringent response, is crucial for survival as well as optimal growth of prokaryotes and, thus, for bacterial pathogenesis and dormancy. In Mycobacterium tuberculosis (Mtb), (p)ppGpp synthesis and degradation are carried out by the bifunctional enzyme MtRel, which consists of 738 residues, including an N-terminal hydrolase- and synthetase-domain (N-terminal domain or NTD) and a C-terminus with a ribosome-binding site. Here, we present the first crystallographic structure of the enzymatically active MtRel NTD determined at 3.7 A resolution. The structure provides insights into the residues of MtRel NTD responsible for nucleotide binding. Small-angle X-ray scattering experiments were performed to investigate the dimeric state of the MtRel NTD and possible substrate-dependent structural alterations.
Crystallographic and solution structure of the N-terminal domain of the Rel protein from Mycobacterium tuberculosis.,Singal B, Balakrishna AM, Nartey W, Manimekalai MSS, Jeyakanthan J, Gruber G FEBS Lett. 2017 Aug;591(15):2323-2337. doi: 10.1002/1873-3468.12739. Epub 2017, Jul 25. PMID:28672070[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Avarbock D, Salem J, Li LS, Wang ZM, Rubin H. Cloning and characterization of a bifunctional RelA/SpoT homologue from Mycobacterium tuberculosis. Gene. 1999 Jun 11;233(1-2):261-9. PMID:10375643
- ↑ Primm TP, Andersen SJ, Mizrahi V, Avarbock D, Rubin H, Barry CE 3rd. The stringent response of Mycobacterium tuberculosis is required for long-term survival. J Bacteriol. 2000 Sep;182(17):4889-98. PMID:10940033
- ↑ Singal B, Balakrishna AM, Nartey W, Manimekalai MSS, Jeyakanthan J, Gruber G. Crystallographic and solution structure of the N-terminal domain of the Rel protein from Mycobacterium tuberculosis. FEBS Lett. 2017 Aug;591(15):2323-2337. doi: 10.1002/1873-3468.12739. Epub 2017, Jul 25. PMID:28672070 doi:http://dx.doi.org/10.1002/1873-3468.12739
