View source for 6lxg


==NMR solution structure of regulatory ACT domain of the Mycobacterium tuberculosis Rel protein==
<StructureSection load='6lxg' size='340' side='right'caption='[[6lxg]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lxg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LXG FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lxg OCA], [https://pdbe.org/6lxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lxg RCSB], [https://www.ebi.ac.uk/pdbsum/6lxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lxg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RELA_MYCTU 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.<ref>PMID:10375643</ref> <ref>PMID:10940033</ref> 
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== Publication Abstract from PubMed ==
The stringent response, regulated by the bifunctional (p)ppGpp synthetase/hydrolase Rel in mycobacteria, is critical for long-term survival of the drug-tolerant dormant state of Mycobacterium tuberculosis. During amino acid starvation, MtRel senses a drop in amino acid concentration and synthesizes the messengers pppGpp and ppGpp, collectively called (p)ppGpp. Here, we investigate the role of the regulatory 'Aspartokinase, Chorismate mutase and TyrA' (ACT) domain in MtRel. Using NMR spectroscopy approaches, we report the high-resolution structure of dimeric MtRel ACT which selectively binds to valine out of all other branched-chain amino acids tested. A set of MtRel ACT mutants were generated to identify the residues required for maintaining the head-to-tail dimer. Through NMR titrations, we determined the crucial residues for binding of valine and show structural rearrangement of the MtRel ACT dimer in the presence of valine. This study suggests the direct involvement of amino acids in (p)ppGpp accumulation mediated by MtRel independent to interactions with stalled ribosomes. Database Structural data are available in the PDB database under the accession number 6LXG.

Atomic structure of, and valine binding to the regulatory ACT domain of the Mycobacterium tuberculosis Rel protein.,Shin J, Singal B, Sony Subramanian Manimekalai M, Wei Chen M, Ragunathan P, Gruber G FEBS J. 2020 Oct 17. doi: 10.1111/febs.15600. PMID:33067840<ref>PMID:33067840</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Gruber G]]
[[Category: Manimekalai MSS]]
[[Category: Shin J]]
[[Category: Singal B]]