2a3u

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of sulbactam bound to E166A variant of SHV-1 beta-lactamase

Structural highlights

2a3u is a 1 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.34Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BLA1_KLEPN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Antibiotic resistance mediated by constantly evolving beta-lactamases is a serious threat to human health. The mechanism of inhibition of these enzymes by therapeutic beta-lactamase inhibitors is probed using a novel approach involving Raman microscopy and x-ray crystallography. We have presented here the high resolution crystal structures of the beta-lactamase inhibitors sulbactam and clavulanic acid bound to the deacylation-deficient E166A variant of SHV-1 beta-lactamase. Our previous Raman measurements have identified the trans-enamine species for both inhibitors and were used to guide the soaking time and concentration to achieve full occupancy of the active sites. The two inhibitor-bound x-ray structures revealed a linear trans-enamine intermediate covalently attached to the active site Ser-70 residue. This intermediate was thought to play a key role in the transient inhibition of class A beta-lactamases. Both the Raman and x-ray data indicated that the clavulanic acid intermediate is decarboxylated. When compared with our previously determined tazobactam-bound inhibitor structure, our new inhibitor-bound structures revealed an increased disorder in the tail region of the inhibitors as well as in the enamine skeleton. The x-ray crystallographic observations correlated with the broadening of the O-C=C-N (enamine) symmetric stretch Raman band near 1595 cm(-1). Band broadening in the sulbactam and clavulanic acid inter-mediates reflected a heterogeneous conformational population that results from variations of torsional angles in the O-(C=O)-C=C=NH-C skeleton. These observations led us to conclude that the conformational stability of the trans-enamine form is critical for their transient inhibitory efficacy.

High resolution crystal structures of the trans-enamine intermediates formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase.,Padayatti PS, Helfand MS, Totir MA, Carey MP, Carey PR, Bonomo RA, van den Akker F J Biol Chem. 2005 Oct 14;280(41):34900-7. Epub 2005 Jul 29. PMID:16055923^[1]

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

References

↑ Padayatti PS, Helfand MS, Totir MA, Carey MP, Carey PR, Bonomo RA, van den Akker F. High resolution crystal structures of the trans-enamine intermediates formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase. J Biol Chem. 2005 Oct 14;280(41):34900-7. Epub 2005 Jul 29. PMID:16055923 doi:10.1074/jbc.M505333200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2a3u"

@@ Line 1: / Line 1: @@
 ==Crystal structure of sulbactam bound to E166A variant of SHV-1 beta-lactamase==
-<StructureSection load='2a3u' size='340' side='right' caption='[[2a3u]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
+<StructureSection load='2a3u' size='340' side='right'caption='[[2a3u]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2a3u]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A3U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A3U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2a3u]] 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=2A3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A3U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TSL:TRANS-ENAMINE+INTERMEDIATE+OF+SULBACTAM'>TSL</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]] 1.34&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rcj|1rcj]], [[2a49|2a49]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=TSL:TRANS-ENAMINE+INTERMEDIATE+OF+SULBACTAM'>TSL</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, shv1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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=2a3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a3u OCA], [https://pdbe.org/2a3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a3u RCSB], [https://www.ebi.ac.uk/pdbsum/2a3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a3u ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=2a3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a3u OCA], [http://pdbe.org/2a3u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a3u RCSB], [http://www.ebi.ac.uk/pdbsum/2a3u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a3u 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/a3/2a3u_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a3/2a3u_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 2a3u" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Beta-lactamase]]
+[[Category: Klebsiella pneumoniae]]
-[[Category: Akker, F van den]]
+[[Category: Large Structures]]
-[[Category: Bonomo, R A]]
+[[Category: Bonomo RA]]
-[[Category: Carey, M P]]
+[[Category: Carey MP]]
-[[Category: Carey, P R]]
+[[Category: Carey PR]]
-[[Category: Helfand, M S]]
+[[Category: Helfand MS]]
-[[Category: Padayatti, P S]]
+[[Category: Padayatti PS]]
-[[Category: Totir, M A]]
+[[Category: Totir MA]]
-[[Category: Beta-lactam hydrolase]]
+[[Category: Van den Akker F]]
-[[Category: Covalent intermediate]]
-[[Category: Detergent binding]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor design]]
-[[Category: Penicillinase]]

2a3u

From Proteopedia

Current revision

Crystal structure of sulbactam bound to E166A variant of SHV-1 beta-lactamase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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