1nnr: Difference between revisions

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{{Seed}}
[[Image:1nnr.png|left|200px]]


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==Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site==
The line below this paragraph, containing "STRUCTURE_1nnr", creates the "Structure Box" on the page.
<StructureSection load='1nnr' size='340' side='right'caption='[[1nnr]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1nnr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NNR FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_1nnr|  PDB=1nnr  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nnr OCA], [https://pdbe.org/1nnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nnr RCSB], [https://www.ebi.ac.uk/pdbsum/1nnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nnr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FOSA_PSEAE FOSA_PSEAE] Metalloglutathione transferase which confers resistance to fosfomycin by catalyzing the addition of glutathione to fosfomycin.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nn/1nnr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nnr ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fosfomycin [(1R,2S)-epoxypropylphosphonic acid] is a simple phosphonate found to have antibacterial activity against both Gram-positive and Gram-negative microorganisms. Early resistance to the clinical use of the antibiotic was linked to a plasmid-encoded resistance protein, FosA, that catalyzes the addition of glutathione to the oxirane ring, rendering the antibiotic inactive. Subsequent studies led to the discovery of a genomically encoded homologue in the pathogen Pseudomonas aeruginosa. The proteins are Mn(II)-dependent enzymes where the metal is proposed to act as a Lewis acid stabilizing the negative charge that develops on the oxirane oxygen in the transition state. Several simple phosphonates, including the antiviral compound phosphonoformate (K(i) = 0.4 +/- 0.1 microM, K(d) approximately 0.2 microM), are shown to be inhibitors of FosA. The crystal structure of FosA from P. aeruginosa with phosphonoformate bound in the active site has been determined at 0.95 A resolution and reveals that the inhibitor forms a five-coordinate complex with the Mn(II) center with a geometry similar to that proposed for the transition state of the reaction. Binding studies show that phosphonoformate has a near-diffusion-controlled on rate (k(on) approximately 10(7)-10(8) M(-1) s(-1)) and an off rate (k(off) = 5 s(-1)) that is slower than that for fosfomycin (k(off) = 30 s(-1)). Taken together, these data suggest that the FosA-catalyzed reaction has a very early transition state and phosphonoformate acts as a minimal transition state analogue inhibitor.


===Crystal structure of a probable fosfomycin resistance protein (PA1129) from Pseudomonas aeruginosa with sulfate present in the active site===
Phosphonoformate: a minimal transition state analogue inhibitor of the fosfomycin resistance protein, FosA.,Rigsby RE, Rife CL, Fillgrove KL, Newcomer ME, Armstrong RN Biochemistry. 2004 Nov 2;43(43):13666-73. PMID:15504029<ref>PMID:15504029</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_15504029}}, adds the Publication Abstract to the page
<div class="pdbe-citations 1nnr" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 15504029 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_15504029}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
1NNR is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_pao1 Pseudomonas aeruginosa pao1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NNR OCA].
[[Category: Pseudomonas aeruginosa PAO1]]
 
[[Category: Armstrong RN]]
==Reference==
[[Category: Newcomer ME]]
<ref group="xtra">PMID:15504029</ref><references group="xtra"/>
[[Category: Pharris RE]]
[[Category: Glutathione transferase]]
[[Category: Rife CL]]
[[Category: Pseudomonas aeruginosa pao1]]
[[Category: Armstrong, R N.]]
[[Category: Newcomer, M E.]]
[[Category: Pharris, R E.]]
[[Category: Rife, C L.]]
[[Category: Manganese binding]]
[[Category: Potassium binding loop]]
 
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Retrieved from "https://proteopedia.org/1nnr"