5kyg
From Proteopedia
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==RAWV_CTD (Loop Structure) of 16S/23S 2'-O-methyltransferase TlyA== | ==RAWV_CTD (Loop Structure) of 16S/23S 2'-O-methyltransferase TlyA== | ||
| - | <StructureSection load='5kyg' size='340' side='right' caption='[[5kyg]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5kyg' size='340' side='right'caption='[[5kyg]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5kyg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KYG OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5kyg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KYG FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kyg OCA], [https://pdbe.org/5kyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kyg RCSB], [https://www.ebi.ac.uk/pdbsum/5kyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kyg ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TLYA_MYCTU TLYA_MYCTU] Acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy (PubMed:25847237). Catalyzes the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA (PubMed:16857584, PubMed:20854656). Is likely involved in ribosomal biogenesis (PubMed:21443791). Also exhibits hemolytic activity in vitro, by binding with and oligomerizing into host cell membranes (PubMed:20854656, PubMed:9611795).<ref>PMID:16857584</ref> <ref>PMID:20854656</ref> <ref>PMID:21443791</ref> <ref>PMID:25847237</ref> <ref>PMID:9611795</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Capreomycin is a potent ribosome-targeting antibiotic that is an essential component of current antituberculosis treatments, particularly in the case of multi-drug resistant Mycobacterium tuberculosis (Mtb). Optimal capreomycin binding and Mtb ribosome inhibition requires ribosomal RNA (rRNA) methylation in both ribosome subunits by TlyA (Rv1694), an enzyme with dual 2'-O-methytransferase and putative hemolytic activities. Despite TlyA's important role in capreomycin sensitivity and identification of inactivating mutations in the corresponding Mtb gene tylA which cause resistance to capreomycin, our current structural and mechanistic understanding of TlyA action remains limited. Here, we present structural and functional analyses of Mtb TlyA interaction with its obligatory cosubstrate for methyltransferase activity, S-adenosyl-L-methionine (SAM). Despite adopting a complete Class I methyltransferase fold containing conserved SAM-binding and catalytic motifs, the isolated TlyA carboxyterminal domain (CTD) exhibits no detectable affinity for SAM. Further analyses identify a tetrapeptide motif (RxWV) in the TlyA interdomain linker as indispensable for cosubstrate binding. Our results also suggest that structural plasticity of the RxWV motif could contribute to TlyA domain interactions as well as specific recognition of its two structurally distinct rRNA targets. Our findings thus reveal a novel motif requirement for SAM binding by TlyA and set the stage for future mechanistic studies of TlyA substrate recognition and modification which underpin Mtb sensitivity to capreomycin. | ||
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| + | A Novel Motif for S-adenosyl-L-methionine Binding by the Ribosomal RNA Methyltransferase TlyA from Mycobacterium tuberculosis.,Witek MA, Kuiper EG, Minten E, Crispell EK, Conn GL J Biol Chem. 2016 Dec 27. pii: jbc.M116.752659. doi: 10.1074/jbc.M116.752659. PMID:28031456<ref>PMID:28031456</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5kyg" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: | + | [[Category: Conn GL]] |
| - | [[Category: | + | [[Category: Kuiper EG]] |
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Current revision
RAWV_CTD (Loop Structure) of 16S/23S 2'-O-methyltransferase TlyA
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