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
The stringent response is critical for the survival of Mycobacterium tuberculosis (Mtb) under nutrient starvation. The mechanism is mediated by a GTP pyrophosphokinase known as Rel, containing N-terminal synthetase and hydrolase domains and C-terminal regulatory domains, which include the TGS domain (ThrRS, GTPase, and SpoT proteins) that has been proposed to activate the synthetase domain via interaction with deacylated tRNA. Here, we present the NMR solution structure of the Mtb Rel TGS domain (MtRel TGS), consisting of five antiparallel beta-strands and one helix-loop-helix motif. The interaction of MtRel TGS with deacylated tRNA is shown, indicating the critical amino acids of MtRel TGS in tRNA binding, and presenting the first structural evidence of MtRel TGS binding to deacylated tRNA in solution in the absence of the translational machinery.
Atomic structure of the regulatory TGS domain of Rel protein from Mycobacterium tuberculosis and its interaction with deacylated tRNA.,Shin J, Singal B, Gruber A, Wong DMK, Ragunathan P, Gruber G FEBS Lett. 2021 Nov 22. doi: 10.1002/1873-3468.14236. PMID:34808002[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
- ↑ Shin J, Singal B, Gruber A, Wong DMK, Ragunathan P, Gruber G. Atomic structure of the regulatory TGS domain of Rel protein from Mycobacterium tuberculosis and its interaction with deacylated tRNA. FEBS Lett. 2021 Nov 22. doi: 10.1002/1873-3468.14236. PMID:34808002 doi:http://dx.doi.org/10.1002/1873-3468.14236