5ypk: Difference between revisions
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==Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI2 complex== | ==Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI2 complex== | ||
<StructureSection load='5ypk' size='340' side='right' caption='[[5ypk]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='5ypk' size='340' side='right'caption='[[5ypk]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ypk]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5ypk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YPK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HIW:(2R,4S)-2-[(1S,2R)-1-CARBOXY-2-HYDROXYPROPYL]-4-[(2-{[(Z)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>HIW</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HIW:(2R,4S)-2-[(1S,2R)-1-CARBOXY-2-HYDROXYPROPYL]-4-[(2-{[(Z)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>HIW</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ypk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypk OCA], [https://pdbe.org/5ypk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ypk RCSB], [https://www.ebi.ac.uk/pdbsum/5ypk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/E5KIY2_ECOLX E5KIY2_ECOLX] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Feng H]] | ||
[[Category: | [[Category: Liu W]] | ||
[[Category: | [[Category: Wang D]] | ||
Latest revision as of 11:34, 22 November 2023
Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI2 complexCrystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI2 complex
Structural highlights
FunctionPublication Abstract from PubMedNew 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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