3p2k

From Proteopedia

(Difference between revisions)

Revision as of 02:09, 5 August 2016

Structure of an antibiotic related Methyltransferase

Structural highlights

3p2k is a 4 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3p2e, 3p2i
Gene:	npmA ("Bacillus coli" Migula 1895)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NPMA_ECOLX] Specifically methylates the N(1) position of adenine 1408 in 16S rRNA. Confers resistance to various aminoglycosides, including kanamycin, neomycin, apramycin, ribostamycin and gentamicin. Methylates only fully assembled 30S subunits.^[1] ^[2] ^[3]

Publication Abstract from PubMed

NpmA, a methyltransferase that confers resistance to aminoglycosides was identified in an Escherichia coli clinical isolate. It belongs to the kanamycin-apramycin methyltransferase (Kam) family and specifically methylates the 16S rRNA at the N1 position of A1408. We determined the structures of apo-NpmA and its complexes with S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.4, 2.7 and 1.68 A, respectively. We generated a number of NpmA variants with alanine substitutions and studied their ability to bind the cofactor, to methylate A1408 in the 30S subunit, and to confer resistance to kanamycin in vivo. Residues D30, W107 and W197 were found to be essential. We have also analyzed the interactions between NpmA and the 30S subunit by footprinting experiments and computational docking. Helices 24, 42 and 44 were found to be the main NpmA-binding site. Both experimental and theoretical analyses suggest that NpmA flips out the target nucleotide A1408 to carry out the methylation. NpmA is plasmid-encoded and can be transferred between pathogenic bacteria; therefore it poses a threat to the successful use of aminoglycosides in clinical practice. The results presented here will assist in the development of specific NpmA inhibitors that could restore the potential of aminoglycoside antibiotics.

Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit.,Husain N, Obranic S, Koscinski L, Seetharaman J, Babic F, Bujnicki JM, Maravic-Vlahovicek G, Sivaraman J Nucleic Acids Res. 2010 Nov 9. PMID:21062819^[4]

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

References

↑ Wachino J, Shibayama K, Kurokawa H, Kimura K, Yamane K, Suzuki S, Shibata N, Ike Y, Arakawa Y. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother. 2007 Dec;51(12):4401-9. Epub 2007 Sep 17. PMID:17875999 doi:http://dx.doi.org/10.1128/AAC.00926-07
↑ Zelinskaya N, Rankin CR, Macmaster R, Savic M, Conn GL. Expression, purification and crystallization of adenosine 1408 aminoglycoside-resistance rRNA methyltransferases for structural studies. Protein Expr Purif. 2011 Jan;75(1):89-94. doi: 10.1016/j.pep.2010.07.005. Epub, 2010 Jul 25. PMID:20667473 doi:http://dx.doi.org/10.1016/j.pep.2010.07.005
↑ Husain N, Obranic S, Koscinski L, Seetharaman J, Babic F, Bujnicki JM, Maravic-Vlahovicek G, Sivaraman J. Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit. Nucleic Acids Res. 2010 Nov 9. PMID:21062819 doi:10.1093/nar/gkq1033
↑ Husain N, Obranic S, Koscinski L, Seetharaman J, Babic F, Bujnicki JM, Maravic-Vlahovicek G, Sivaraman J. Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit. Nucleic Acids Res. 2010 Nov 9. PMID:21062819 doi:10.1093/nar/gkq1033

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/3p2k"

@@ Line 1: / Line 1: @@
 ==Structure of an antibiotic related Methyltransferase==
 <StructureSection load='3p2k' size='340' side='right' caption='[[3p2k]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3p2k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3p2k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P2K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3p2e|3p2e]], [[3p2i|3p2i]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">npmA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">npmA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=3p2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p2k RCSB], [http://www.ebi.ac.uk/pdbsum/3p2k PDBsum]</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=3p2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p2k OCA], [http://pdbe.org/3p2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p2k RCSB], [http://www.ebi.ac.uk/pdbsum/3p2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p2k ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NPMA_ECOLX NPMA_ECOLX]] Specifically methylates the N(1) position of adenine 1408 in 16S rRNA. Confers resistance to various aminoglycosides, including kanamycin, neomycin, apramycin, ribostamycin and gentamicin. Methylates only fully assembled 30S subunits.<ref>PMID:17875999</ref> <ref>PMID:20667473</ref> <ref>PMID:21062819</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3p2k" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Escherichia coli]]
+[[Category: Bacillus coli migula 1895]]
 [[Category: Husain, N]]
 [[Category: Sivaraman, J]]

3p2k

From Proteopedia

Revision as of 02:09, 5 August 2016

Structure of an antibiotic related Methyltransferase

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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