4nnk

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==Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide==
==Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide==
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<StructureSection load='4nnk' size='340' side='right' caption='[[4nnk]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
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<StructureSection load='4nnk' size='340' side='right'caption='[[4nnk]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4nnk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NNK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NNK FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4nnk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NNK FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nng|4nng]], [[4nnh|4nnh]], [[4nni|4nni]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nnk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nnk RCSB], [http://www.ebi.ac.uk/pdbsum/4nnk PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nnk OCA], [https://pdbe.org/4nnk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nnk RCSB], [https://www.ebi.ac.uk/pdbsum/4nnk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nnk ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/RS1_MYCTU RS1_MYCTU]] Binds mRNA; thus facilitating recognition of the initiation point. It is needed to translate mRNA with a short Shine-Dalgarno (SD) purine-rich sequence (By similarity).
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[https://www.uniprot.org/uniprot/RS1_MYCTU RS1_MYCTU] Binds mRNA; thus facilitating recognition of the initiation point. It is needed to translate mRNA with a short Shine-Dalgarno (SD) purine-rich sequence (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.
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Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide.,Yang J, Liu Y, Bi J, Cai Q, Liao X, Li W, Guo C, Zhang Q, Lin T, Zhao Y, Wang H, Liu J, Zhang X, Lin D Mol Microbiol. 2015 Mar;95(5):791-803. doi: 10.1111/mmi.12892. Epub 2015 Jan 16. PMID:25430994<ref>PMID:25430994</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
*[[Ribosomal protein S1|Ribosomal protein S1]]
*[[Ribosomal protein S1|Ribosomal protein S1]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Cai, Q]]
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[[Category: Large Structures]]
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[[Category: Lin, D]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Liu, Y]]
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[[Category: Cai Q]]
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[[Category: Yang, J]]
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[[Category: Lin D]]
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[[Category: Beta barrel]]
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[[Category: Liu Y]]
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[[Category: Ribosomal protein]]
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[[Category: Yang J]]

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Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide

PDB ID 4nnk

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