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'''Unreleased structure'''


The entry 4nnh is ON HOLD  until Paper Publication
==Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide==
<StructureSection load='4nnh' size='340' side='right'caption='[[4nnh]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nnh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NNH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#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=4nnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nnh OCA], [https://pdbe.org/4nnh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nnh RCSB], [https://www.ebi.ac.uk/pdbsum/4nnh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nnh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RS1_MYCS2 RS1_MYCS2] Binds mRNA, facilitating recognition of most mRNAs by the 30S ribosomal subunit during translation initiation (By similarity). Plays a role in trans-translation; binds tmRNA (the product of the ssrA gene) (PubMed:25430994). Binds very poorly to pyrazinoic acid (POA), the active form of the prodrug pyrazinamide (PZA); POA does not disrupt trans-translation in this organism (PubMed:21835980). M.smegmatis is resistant to the antibiotic PZA (PubMed:25430994). In trans-translation Ala-aminoacylated transfer-messenger RNA (tmRNA, product of the ssrA gene; the 2 termini fold to resemble tRNA(Ala) while it encodes a short internal open reading frame (the tag peptide)) acts like a tRNA, entering the A-site of the ribosome and displacing the stalled mRNA (which is subsequently degraded). The ribosome then switches to translate the ORF on the tmRNA, the nascent peptide is terminated with the 'tag peptide' encoded by the tmRNA and thus targeted for degradation.[UniProtKB:P0AG67]<ref>PMID:21835980</ref> <ref>PMID:25430994</ref>


Authors: Yang, J., Liu, Y., Cai, Q., Lin, D.
==See Also==
 
*[[Ribosomal protein S1|Ribosomal protein S1]]
Description: The Structure Basis: a Novel Target RpsA From Mycobacterium Tuberculosis Recognition of Pyrazinoic Acid for Inhibiting Trans-translation
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Cai Q]]
[[Category: Lin D]]
[[Category: Liu Y]]
[[Category: Yang J]]

Latest revision as of 11:57, 20 March 2024

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

Structural highlights

4nnh is a 2 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RS1_MYCS2 Binds mRNA, facilitating recognition of most mRNAs by the 30S ribosomal subunit during translation initiation (By similarity). Plays a role in trans-translation; binds tmRNA (the product of the ssrA gene) (PubMed:25430994). Binds very poorly to pyrazinoic acid (POA), the active form of the prodrug pyrazinamide (PZA); POA does not disrupt trans-translation in this organism (PubMed:21835980). M.smegmatis is resistant to the antibiotic PZA (PubMed:25430994). In trans-translation Ala-aminoacylated transfer-messenger RNA (tmRNA, product of the ssrA gene; the 2 termini fold to resemble tRNA(Ala) while it encodes a short internal open reading frame (the tag peptide)) acts like a tRNA, entering the A-site of the ribosome and displacing the stalled mRNA (which is subsequently degraded). The ribosome then switches to translate the ORF on the tmRNA, the nascent peptide is terminated with the 'tag peptide' encoded by the tmRNA and thus targeted for degradation.[UniProtKB:P0AG67][1] [2]

See Also

References

  1. ↑ Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. doi: 10.1126/science.1208813. Epub 2011 , Aug 11. PMID:21835980 doi:http://dx.doi.org/10.1126/science.1208813
  2. ↑ 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. Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide. Mol Microbiol. 2015 Mar;95(5):791-803. doi: 10.1111/mmi.12892. Epub 2015 Jan 16. PMID:25430994 doi:http://dx.doi.org/10.1111/mmi.12892

4nnh, resolution 2.30Å

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