View source for 8wx0


==PNPase of M.tuberculosis with its RNA substrate==
<StructureSection load='8wx0' size='340' side='right'caption='[[8wx0]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8wx0]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WX0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WX0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</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=8wx0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wx0 OCA], [https://pdbe.org/8wx0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wx0 RCSB], [https://www.ebi.ac.uk/pdbsum/8wx0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wx0 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
As one of the oldest infectious diseases in the world, tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), which can attack various organs of the human body. Up to now, drug-resistant TB continues to be a public health threat. Pyrazinamide (PZA) is regarded as a sterilizing drug in the treatment of TB due to its distinct ability to target Mtb persisters. Previously we demonstrated that a D67N mutation in Mycobacterium tuberculosis polynucleotide phosphorylase (MtbPNPase, Rv2783c) confers resistance to PZA and Rv2783c is a potential target for PZA, but the mechanism leading to PZA resistance remains unclear. To gain further insight into the MtbPNPase, we determined the cryo-EM structures of apo Rv2783c, its mutant form and its complex with RNA. Our studies revealed the Rv2783c structure at atomic resolution and identified its enzymatic functional groups essential for its phosphorylase activities. We also investigated the molecular mechanisms underlying the resistance to PZA conferred by the mutation. Our research findings provide structural and functional insights enabling the development of new anti-tuberculosis drugs.

Cryo-EM structures of Mycobacterium tuberculosis polynucleotide phosphorylase suggest a potential mechanism for its RNA substrate degradation.,Wang N, Sheng Y, Liu Y, Guo Y, He J, Liu J Arch Biochem Biophys. 2024 Apr;754:109917. doi: 10.1016/j.abb.2024.109917. Epub , 2024 Feb 22. PMID:38395123<ref>PMID:38395123</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Synthetic construct]]
[[Category: Sheng YN]]
[[Category: Wang N]]