4fd8

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(Difference between revisions)

Revision as of 10:52, 11 August 2016

Structure of apo S70C SHV beta-lactamase

Structural highlights

4fd8 is a 1 chain structure with sequence from "bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4fcf
Gene:	bla, shv1 ("Bacillus pneumoniae" (Schroeter 1886) Flugge 1886)
Activity:	Beta-lactamase, with EC number 3.5.2.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The rise of inhibitor-resistant and other beta-lactamase variants is generating an interest in developing new beta-lactamase inhibitors to complement currently available antibiotics. To gain insight into the chemistry of recognition, we determined the crystal structure of the inhibitor pre-acylation complex of sulbactam, a clinical beta-lactamase inhibitor, bound in the active site of the S70C variant of SHV-1 beta-lactamase that is normally present in Klebsiella pneumoniae. The S70C mutation was designed to affect the reactivity of that catalytic residue and to allow for capture of the pre-acylation complex. Unexpectedly, the 1.45A resolution inhibitor complex structure revealed that residue C70 is involved in a sulfenamide bond with K73. Such a covalent bond is not present in the wild type SHV-1 or in an apo S70C structure also determined in this study. This bond likely contributed significantly to obtaining the pre-acylation complex with sulbactam due to further decreased reactivity towards substrates. The intact sulbactam is positioned in the active site such that its carboxyl moiety interacts with R244, S130, and T235 and its carbonyl moiety is situated in the oxyanion hole. To our knowledge, in addition to being the first pre-acylation inhibitor beta-lactamase complex, this is also the first observation of a sulfenamide bond between a cysteine and lysine in an active site. Our results could therefore not only aid structure-based inhibitor design efforts in class A beta-lactamases, but the sulfenamide-bond forming approach to yield pre-acylation complexes could also be applied to other classes of beta-lactamases and penicillin-binding proteins with the SXXK motif.

Crystal structure of a pre-acylation complex of the beta-lactamase inhibitor, sulbactam, bound to a sulfenamide bond containing thiol-beta-lactamase.,Rodkey EA, Drawz SM, Sampson JM, Bethel CR, Bonomo RA, van den Akker F J Am Chem Soc. 2012 Sep 13. PMID:22974281^[1]

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

References

↑ Rodkey EA, Drawz SM, Sampson JM, Bethel CR, Bonomo RA, van den Akker F. Crystal structure of a pre-acylation complex of the beta-lactamase inhibitor, sulbactam, bound to a sulfenamide bond containing thiol-beta-lactamase. J Am Chem Soc. 2012 Sep 13. PMID:22974281 doi:10.1021/ja3073676

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4fd8"

@@ Line 1: / Line 1: @@
 ==Structure of apo S70C SHV beta-lactamase==
 <StructureSection load='4fd8' size='340' side='right' caption='[[4fd8]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4fd8]] 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=4FD8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FD8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4fd8]] 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=4FD8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FD8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fcf|4fcf]]</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 Klebsiella pneumoniae])</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='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=4fd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fd8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fd8 RCSB], [http://www.ebi.ac.uk/pdbsum/4fd8 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=4fd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fd8 OCA], [http://pdbe.org/4fd8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fd8 RCSB], [http://www.ebi.ac.uk/pdbsum/4fd8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fd8 ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4fd8" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Beta-lactamase]]
-[[Category: Klebsiella pneumoniae]]
 [[Category: Akker, F van den]]
 [[Category: Rodkey, E A]]

4fd8

From Proteopedia

Revision as of 10:52, 11 August 2016

Structure of apo S70C SHV beta-lactamase

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

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