4c1f: Difference between revisions
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==Crystal structure of the metallo-beta-lactamase IMP-1 with L-captopril== | |||
<StructureSection load='4c1f' size='340' side='right'caption='[[4c1f]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4c1f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C1F 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]] 2.01Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=X8Z:L-CAPTOPRIL'>X8Z</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4c1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c1f OCA], [https://pdbe.org/4c1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c1f RCSB], [https://www.ebi.ac.uk/pdbsum/4c1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c1f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-beta-lactamases (MBLs). MBLs are of increasing concern because they catalyse the hydrolysis of almost all beta-lactam antibiotics, including recent generation carbapenems. Clinically useful serine-beta-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. l-Captopril, used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating to the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High resolution crystal structures of three MBLs (IMP-1, BcII and VIM-2) in complex with either l-or d-captopril stereoisomers reveal correlations between the binding modes and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other MBL mediated resistant infections. | |||
Structural basis of metallo-beta-lactamase inhibition by captopril stereoisomers.,Brem J, van Berkel SS, Zollman D, Lee SY, Gileadi O, McHugh PJ, Walsh TR, McDonough MA, Schofield CJ Antimicrob Agents Chemother. 2015 Oct 19. pii: AAC.01335-15. PMID:26482303<ref>PMID:26482303</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4c1f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Serratia marcescens]] | |||
[[Category: Brem J]] | |||
[[Category: McDonough MA]] | |||
[[Category: Schofield CJ]] | |||
[[Category: Zollman D]] | |||
[[Category: Van Berkel SS]] | |||
Latest revision as of 15:01, 20 December 2023
Crystal structure of the metallo-beta-lactamase IMP-1 with L-captoprilCrystal structure of the metallo-beta-lactamase IMP-1 with L-captopril
Structural highlights
FunctionBLAB_SERMA Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems. Publication Abstract from PubMedbeta-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-beta-lactamases (MBLs). MBLs are of increasing concern because they catalyse the hydrolysis of almost all beta-lactam antibiotics, including recent generation carbapenems. Clinically useful serine-beta-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. l-Captopril, used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating to the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High resolution crystal structures of three MBLs (IMP-1, BcII and VIM-2) in complex with either l-or d-captopril stereoisomers reveal correlations between the binding modes and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other MBL mediated resistant infections. Structural basis of metallo-beta-lactamase inhibition by captopril stereoisomers.,Brem J, van Berkel SS, Zollman D, Lee SY, Gileadi O, McHugh PJ, Walsh TR, McDonough MA, Schofield CJ Antimicrob Agents Chemother. 2015 Oct 19. pii: AAC.01335-15. PMID:26482303[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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