6dmh

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==A multiconformer ligand model of acylenzyme intermediate of meropenem bound to an SFC-1 E166A mutant==
==A multiconformer ligand model of acylenzyme intermediate of meropenem bound to an SFC-1 E166A mutant==
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<StructureSection load='6dmh' size='340' side='right' caption='[[6dmh]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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<StructureSection load='6dmh' size='340' side='right'caption='[[6dmh]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6dmh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DMH FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6dmh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_fonticola Serratia fonticola]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DMH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</scene>, <scene name='pdbligand=MER:(4R,5S)-3-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>MER</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ev4|4ev4]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmh OCA], [https://pdbe.org/6dmh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dmh RCSB], [https://www.ebi.ac.uk/pdbsum/6dmh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmh ProSAT]</span></td></tr>
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<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>
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<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=6dmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmh OCA], [http://pdbe.org/6dmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dmh RCSB], [http://www.ebi.ac.uk/pdbsum/6dmh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmh ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q6JP75_SERFO Q6JP75_SERFO]
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Proteins and ligands sample a conformational ensemble that governs molecular recognition, activity, and dissociation. In structure-based drug design, access to this conformational ensemble is critical to understand the balance between entropy and enthalpy in lead optimization. However, ligand conformational heterogeneity is currently severely underreported in crystal structures in the Protein Data Bank, owing in part to a lack of automated and unbiased procedures to model an ensemble of protein-ligand states into X-ray data. Here, we designed a computational method, qFit-ligand, to automatically resolve conformationally averaged ligand heterogeneity in crystal structures, and applied it to a large set of protein receptor-ligand complexes. In an analysis of the cancer related BRD4 domain, we found that up to 29% of protein crystal structures bound with drug-like molecules present evidence of unmodeled, averaged, relatively iso-energetic conformations in ligand-receptor interactions. In many retrospective cases, these alternate conformations were adventitiously exploited to guide compound design, resulting in improved potency or selectivity. Combining qFit-ligand with high-throughput screening or multi-temperature crystallography could therefore augment the structure-based drug design toolbox.
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qFit-ligand reveals widespread conformational heterogeneity of drug-like molecules in X-ray electron density maps.,van Zundert G, Hudson BM, de Oliveira S, Keedy DA, Fonseca R, Heliou A, Suresh P, Borrelli K, Day T, Fraser J, van den Bedem H J Med Chem. 2018 Nov 20. doi: 10.1021/acs.jmedchem.8b01292. PMID:30457858<ref>PMID:30457858</ref>
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==See Also==
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6dmh" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Beta-lactamase]]
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[[Category: Large Structures]]
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[[Category: Bedem, H van den]]
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[[Category: Serratia fonticola]]
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[[Category: Borrelli, K]]
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[[Category: Borrelli K]]
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[[Category: Day, T]]
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[[Category: Day T]]
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[[Category: Fonseca, R]]
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[[Category: Fonseca R]]
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[[Category: Fraser, J S]]
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[[Category: Fraser JS]]
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[[Category: Heliou, A]]
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[[Category: Heliou A]]
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[[Category: Hudson, B M]]
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[[Category: Hudson BM]]
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[[Category: Keedy, D]]
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[[Category: Keedy D]]
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[[Category: Suresh, P]]
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[[Category: Suresh P]]
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[[Category: Zundert, G van]]
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[[Category: Van Zundert G]]
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[[Category: Antibiotic]]
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[[Category: Van den Bedem H]]
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[[Category: Complex]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Multi conformer model]]
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Current revision

A multiconformer ligand model of acylenzyme intermediate of meropenem bound to an SFC-1 E166A mutant

PDB ID 6dmh

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