5ypi: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 5ypi is ~~ON HOLD until Paper~~ Publication

==Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI1 complex==

== Structural highlights ==

<table><tr><td colspan='2'>[[5ypi]] 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=5YPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YPI 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]] 2.3Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=5ypi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypi OCA], [https://pdbe.org/5ypi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ypi RCSB], [https://www.ebi.ac.uk/pdbsum/5ypi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypi ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/E5KIY2_ECOLX E5KIY2_ECOLX]

== 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.

~~Authors~~:

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>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]

*[[Sequestosome|Sequestosome]]

== References ==

__TOC__

</StructureSection>

[[Category: Escherichia coli]]

[[Category: Large Structures]]

[[Category: Feng H]]

[[Category: Liu W]]

[[Category: Wang D]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ypi is ON HOLD  until Paper Publication
+==Crystal structure of NDM-1 bound to hydrolyzed imipenem representing an EI1 complex==
+<StructureSection load='5ypi' size='340' side='right'caption='[[5ypi]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ypi]] 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=5YPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YPI 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=5ypi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypi OCA], [https://pdbe.org/5ypi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ypi RCSB], [https://www.ebi.ac.uk/pdbsum/5ypi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypi ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/E5KIY2_ECOLX E5KIY2_ECOLX]
+<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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5ypi" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
+*[[Sequestosome|Sequestosome]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli]]
+[[Category: Large Structures]]
+[[Category: Feng H]]
+[[Category: Liu W]]
+[[Category: Wang D]]