5ks2

From Proteopedia

(Difference between revisions)

Current revision

RAWV_CTD (Helix form) of 16S/23S 2'-O-methyltransferase TlyA

Structural highlights

5ks2 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.18Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4] ^[5]

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.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Johansen SK, Maus CE, Plikaytis BB, Douthwaite S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173-82. PMID:16857584 doi:http://dx.doi.org/10.1016/j.molcel.2006.05.044
↑ Rahman A, Srivastava SS, Sneh A, Ahmed N, Krishnasastry MV. Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: a non-conventional hemolysin and a ribosomal RNA methyl transferase. BMC Biochem. 2010 Sep 20;11:35. doi: 10.1186/1471-2091-11-35. PMID:20854656 doi:http://dx.doi.org/10.1186/1471-2091-11-35
↑ Arenas NE, Salazar LM, Soto CY, Vizcaino C, Patarroyo ME, Patarroyo MA, Gomez A. Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: possible misannotation of this tubercle bacilli-hemolysin. BMC Struct Biol. 2011 Mar 28;11:16. doi: 10.1186/1472-6807-11-16. PMID:21443791 doi:http://dx.doi.org/10.1186/1472-6807-11-16
↑ Rahman MA, Sobia P, Dwivedi VP, Bhawsar A, Singh DK, Sharma P, Moodley P, Van Kaer L, Bishai WR, Das G. Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis. J Biol Chem. 2015 Jun 5;290(23):14407-17. doi: 10.1074/jbc.M115.653600. Epub 2015, Apr 6. PMID:25847237 doi:http://dx.doi.org/10.1074/jbc.M115.653600
↑ Wren BW, Stabler RA, Das SS, Butcher PD, Mangan JA, Clarke JD, Casali N, Parish T, Stoker NG. Characterization of a haemolysin from Mycobacterium tuberculosis with homology to a virulence factor of Serpulina hyodysenteriae. Microbiology. 1998 May;144 ( Pt 5):1205-11. PMID:9611795
↑ Witek MA, Kuiper EG, Minten E, Crispell EK, Conn GL. A Novel Motif for S-adenosyl-L-methionine Binding by the Ribosomal RNA Methyltransferase TlyA from Mycobacterium tuberculosis. J Biol Chem. 2016 Dec 27. pii: jbc.M116.752659. doi: 10.1074/jbc.M116.752659. PMID:28031456 doi:http://dx.doi.org/10.1074/jbc.M116.752659

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ks2"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Conn GL | Kuiper EG

@@ Line 3: / Line 3: @@
 <StructureSection load='5ks2' size='340' side='right'caption='[[5ks2]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ks2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KS2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ks2]] 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=5KS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KS2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eov|5eov]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tlyA, Rv1694 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5ks2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ks2 OCA], [https://pdbe.org/5ks2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ks2 RCSB], [https://www.ebi.ac.uk/pdbsum/5ks2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ks2 ProSAT]</span></td></tr>
-<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=5ks2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ks2 OCA], [http://pdbe.org/5ks2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ks2 RCSB], [http://www.ebi.ac.uk/pdbsum/5ks2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ks2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 25: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Conn, G L]]
+[[Category: Conn GL]]
-[[Category: Kuiper, E G]]
+[[Category: Kuiper EG]]
-[[Category: Antibiotic sensitivity]]
-[[Category: Hemolysin]]
-[[Category: Methyltransferase]]
-[[Category: Ribosome]]
-[[Category: Transferase]]

5ks2

From Proteopedia

Current revision

RAWV_CTD (Helix form) of 16S/23S 2'-O-methyltransferase TlyA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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