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5wih
From Proteopedia
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==Structure of New Delhi Metallo-Beta-lactamase 12 (NDM-12)== | ==Structure of New Delhi Metallo-Beta-lactamase 12 (NDM-12)== | ||
| - | <StructureSection load='5wih' size='340' side='right' caption='[[5wih]], [[Resolution|resolution]] 1.35Å' scene=''> | + | <StructureSection load='5wih' size='340' side='right'caption='[[5wih]], [[Resolution|resolution]] 1.35Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5wih]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WIH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wih]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WIH FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaNDM-12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=5wih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wih OCA], [http://pdbe.org/5wih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wih RCSB], [http://www.ebi.ac.uk/pdbsum/5wih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wih 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=5wih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wih OCA], [http://pdbe.org/5wih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wih RCSB], [http://www.ebi.ac.uk/pdbsum/5wih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wih ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Use and misuse of antibiotics have driven the evolution of serine beta-lactamases to better recognize new generations of beta-lactam drugs, but the selective pressures driving evolution of metallo-beta-lactamases are less clear. Here, we present evidence that New Delhi metallo-beta-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites. Each of the clinical variants is shown to be progressively more thermostable and to bind zinc(II) more tightly than NDM-1, but a selective enhancement of penam turnover at low zinc(II) concentrations indicates that most of the improvement derives from catalysis rather than stability. X-ray crystallography of NDM-4 and NDM-12, as well as bioinorganic spectroscopy of dizinc(II), zinc(II)/cobalt(II), and dicobalt(II) metalloforms probe the mechanism of enhanced resistance and reveal perturbations of the dinuclear metal cluster that underlie improved catalysis. These studies support the proposal that zinc(II) scarcity, rather than changes in antibiotic structure, is driving the evolution of new NDM variants in clinical settings. | ||
| + | |||
| + | Clinical Variants of New Delhi Metallo-beta-Lactamase Are Evolving To Overcome Zinc Scarcity.,Stewart AC, Bethel CR, VanPelt J, Bergstrom A, Cheng Z, Miller CG, Williams C, Poth R, Morris M, Lahey O, Nix JC, Tierney DL, Page RC, Crowder MW, Bonomo RA, Fast W ACS Infect Dis. 2017 Dec 8;3(12):927-940. doi: 10.1021/acsinfecdis.7b00128. Epub , 2017 Oct 11. PMID:28965402<ref>PMID:28965402</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5wih" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus coli migula 1895]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Page, R C]] | [[Category: Page, R C]] | ||
[[Category: VanPelt, J]] | [[Category: VanPelt, J]] | ||
Revision as of 09:01, 1 May 2019
Structure of New Delhi Metallo-Beta-lactamase 12 (NDM-12)
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