2h5s: Difference between revisions

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[[Image:2h5s.png|left|200px]]


{{STRUCTURE_2h5s| PDB=2h5s | SCENE= }}
==SA2-13 penam sulfone complexed to wt SHV-1 beta-lactamase==
<StructureSection load='2h5s' size='340' side='right'caption='[[2h5s]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2h5s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H5S FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=SA2:(3R)-4-[(4-CARBOXYBUTANOYL)OXY]-N-[(1E)-3-OXOPROP-1-EN-1-YL]-3-SULFINO-D-VALINE'>SA2</scene></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=2h5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5s OCA], [https://pdbe.org/2h5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h5s RCSB], [https://www.ebi.ac.uk/pdbsum/2h5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h5s ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN]
== 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/h5/2h5s_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=2h5s ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
beta-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of beta-lactamases that are capable of hydrolyzing our most potent beta-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors.


===SA2-13 penam sulfone complexed to wt SHV-1 beta-lactamase===
Rational design of a beta-lactamase inhibitor achieved via stabilization of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a penam sulfone.,Padayatti PS, Sheri A, Totir MA, Helfand MS, Carey MP, Anderson VE, Carey PR, Bethel CR, Bonomo RA, Buynak JD, van den Akker F J Am Chem Soc. 2006 Oct 11;128(40):13235-42. PMID:17017804<ref>PMID:17017804</ref>


{{ABSTRACT_PUBMED_17017804}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 2h5s" style="background-color:#fffaf0;"></div>
[[2h5s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5S OCA].


==See Also==
==See Also==
*[[Beta-lactamase|Beta-lactamase]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:017017804</ref><references group="xtra"/>
__TOC__
[[Category: Beta-lactamase]]
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Klebsiella pneumoniae]]
[[Category: Akker, F van den.]]
[[Category: Large Structures]]
[[Category: Padayatti, P S.]]
[[Category: Padayatti PS]]
[[Category: Beta-lactamase inhibitor]]
[[Category: Van den Akker F]]
[[Category: Drug design]]
[[Category: Hydrolase]]
Retrieved from "https://proteopedia.org/2h5s"