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5ypi
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI1 complex== | |
| + | <StructureSection load='5ypi' size='340' side='right' caption='[[5ypi]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ypi]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YPI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YPI FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8YF:(2R)-2-[(2S,3R)-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-(2-methanimidamidoethylsulfanyl)-2,3-dihydro-1H-pyrrole-5-carboxylic+acid'>8YF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ypi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypi OCA], [http://pdbe.org/5ypi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ypi RCSB], [http://www.ebi.ac.uk/pdbsum/5ypi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | New Delhi metallo-beta-lactamases (NDMs), the recent additions to metallo-beta-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of beta-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 A, together with NMR spectra monitoring meropenem hydrolysis. Three enzyme-intermediate/product derivatives, EI1, EI2, and EP, are trapped in these crystals. Our structural data reveal double-bond tautomerization from Delta(2) to Delta(1), absence of a bridging water molecule and an exclusive beta-diastereomeric product, all suggesting that the hydrolytic intermediates are protonated by a bulky water molecule incoming from the beta-face. These results strongly suggest a distinct mechanism of NDM-1-catalyzed carbapenem hydrolysis from that of penicillin or cephalosporin hydrolysis, which may provide a novel rationale for design of mechanism-based inhibitors. | ||
| - | + | The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.,Feng H, Liu X, Wang S, Fleming J, Wang DC, Liu W Nat Commun. 2017 Dec 21;8(1):2242. doi: 10.1038/s41467-017-02339-w. PMID:29269938<ref>PMID:29269938</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5ypi" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Feng, H]] | ||
| + | [[Category: Liu, W]] | ||
| + | [[Category: Wang, D]] | ||
| + | [[Category: Ei1 complex]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Imipenem]] | ||
| + | [[Category: Ndm-1]] | ||
Revision as of 07:22, 22 February 2018
Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI1 complex
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Categories: Feng, H | Liu, W | Wang, D | Ei1 complex | Hydrolase | Imipenem | Ndm-1
