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| | <StructureSection load='4c1g' size='340' side='right'caption='[[4c1g]], [[Resolution|resolution]] 1.71Å' scene=''> | | <StructureSection load='4c1g' size='340' side='right'caption='[[4c1g]], [[Resolution|resolution]] 1.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c1g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C1G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C1G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c1g]] 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=4C1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C1G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MCO:1-(3-MERCAPTO-2-METHYL-PROPIONYL)-PYRROLIDINE-2-CARBOXYLIC+ACID'>MCO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.714Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bz3|4bz3]], [[4c09|4c09]], [[4c1c|4c1c]], [[4c1d|4c1d]], [[4c1e|4c1e]], [[4c1f|4c1f]], [[4c1h|4c1h]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MCO:1-(3-MERCAPTO-2-METHYL-PROPIONYL)-PYRROLIDINE-2-CARBOXYLIC+ACID'>MCO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4c1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c1g OCA], [https://pdbe.org/4c1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c1g RCSB], [https://www.ebi.ac.uk/pdbsum/4c1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c1g ProSAT]</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=4c1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c1g OCA], [http://pdbe.org/4c1g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c1g RCSB], [http://www.ebi.ac.uk/pdbsum/4c1g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c1g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA]] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Berkel, S S.van]] | + | [[Category: Serratia marcescens]] |
| - | [[Category: Brem, J]] | + | [[Category: Brem J]] |
| - | [[Category: McDonough, M A]] | + | [[Category: McDonough MA]] |
| - | [[Category: Schofield, C J]] | + | [[Category: Schofield CJ]] |
| - | [[Category: Zollman, D]] | + | [[Category: Zollman D]] |
| - | [[Category: Antibiotic resistance]] | + | [[Category: Van Berkel SS]] |
| - | [[Category: Hydrolase]]
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| Structural highlights
Function
BLAB_SERMA Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brem J, van Berkel SS, Zollman D, Lee SY, Gileadi O, McHugh PJ, Walsh TR, McDonough MA, Schofield CJ. Structural basis of metallo-beta-lactamase inhibition by captopril stereoisomers. Antimicrob Agents Chemother. 2015 Oct 19. pii: AAC.01335-15. PMID:26482303 doi:http://dx.doi.org/10.1128/AAC.01335-15
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