3fv7: Difference between revisions

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-{{Seed}}
-[[Image:3fv7.png|left|200px]]
-<!--
+==OXA-24 beta-lactamase complex with SA4-44 inhibitor==
-The line below this paragraph, containing "STRUCTURE_3fv7", creates the "Structure Box" on the page.
+<StructureSection load='3fv7' size='340' side='right'caption='[[3fv7]], [[Resolution|resolution]] 2.00&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'>[[3fv7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FV7 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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MXS:(2S)-2-[[2-METHANOYL-7-(METHOXYCARBONYLAMINO)INDOLIZIN-3-YL]AMINO]-3-METHYL-3-SULFINO-BUTANOIC+ACID'>MXS</scene></td></tr>
-{{STRUCTURE_3fv7|  PDB=3fv7  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fv7 OCA], [https://pdbe.org/3fv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fv7 RCSB], [https://www.ebi.ac.uk/pdbsum/3fv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fv7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8RLA6_ACIBA Q8RLA6_ACIBA]
+== 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/fv/3fv7_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=3fv7 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Class D beta-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial beta-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel beta-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2'-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important beta-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 beta-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC(50) values against OXA-24 and two OXA-24 beta-lactamase variants ranged from 10 +/- 1 (4 vs WT) to 338 +/- 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest K(i) (500 +/- 80 nM vs WT), and 1 possessed the highest inactivation efficiency (k(inact)/K(i) = 0.21 +/- 0.02 muM(-1) s(-1)). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 A) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2'-substituted penicillin sulfones are effective mechanism-based inactivators of class D beta-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D beta-lactamases is proposed.
-===OXA-24 beta-lactamase complex with SA4-44 inhibitor===
+Design, synthesis, and crystal structures of 6-alkylidene-2'-substituted penicillanic acid sulfones as potent inhibitors of Acinetobacter baumannii OXA-24 carbapenemase.,Bou G, Santillana E, Sheri A, Beceiro A, Sampson JM, Kalp M, Bethel CR, Distler AM, Drawz SM, Pagadala SR, van den Akker F, Bonomo RA, Romero A, Buynak JD J Am Chem Soc. 2010 Sep 29;132(38):13320-31. PMID:20822105<ref>PMID:20822105</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3fv7" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20822105}}, adds the Publication Abstract to the page
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20822105 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20822105}}
+__TOC__
+</StructureSection>
-==About this Structure==
-FV7 is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FV7 OCA].
-==Reference==
-<ref group="xtra">PMID:20822105</ref><ref group="xtra">PMID:17374723</ref><references group="xtra"/>
 [[Category: Acinetobacter baumannii]]
-[[Category: Beta-lactamase]]
+[[Category: Large Structures]]
-[[Category: Akker, F Van den.]]
+[[Category: Beceiro A]]
-[[Category: Beceiro, A.]]
+[[Category: Bethel CR]]
-[[Category: Bethel, C R.]]
+[[Category: Bonomo RA]]
-[[Category: Bonomo, R A.]]
+[[Category: Bou G]]
-[[Category: Bou, G.]]
+[[Category: Buynak JD]]
-[[Category: Buynak, J D.]]
+[[Category: Distler AM]]
-[[Category: Distler, A M.]]
+[[Category: Drawz SM]]
-[[Category: Drawz, S M.]]
+[[Category: Kalp M]]
-[[Category: Kalp, M.]]
+[[Category: Pagadala SR]]
-[[Category: Pagadala, S R.]]
+[[Category: Romero A]]
-[[Category: Romero, A.]]
+[[Category: Sampson JM]]
-[[Category: Sampson, J M.]]
+[[Category: Santillana E]]
-[[Category: Santillana, E.]]
+[[Category: Sheri A]]
-[[Category: Sheri, A.]]
+[[Category: Van den Akker F]]
-[[Category: B-lactamase]]
-[[Category: Carbapenem]]
-[[Category: Enzyme mechanism]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 13 10:22:41 2010''