7chv
From Proteopedia
(Difference between revisions)
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==Metallo-Beta-Lactamase VIM-2 in complex with 1-benzyl-1H-imidazole-2-carboxylic acid== | ==Metallo-Beta-Lactamase VIM-2 in complex with 1-benzyl-1H-imidazole-2-carboxylic acid== | ||
| - | <StructureSection load='7chv' size='340' side='right'caption='[[7chv]]' scene=''> | + | <StructureSection load='7chv' size='340' side='right'caption='[[7chv]], [[Resolution|resolution]] 2.17Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CHV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7chv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CHV FirstGlance]. <br> |
| - | </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=7chv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7chv OCA], [https://pdbe.org/7chv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7chv RCSB], [https://www.ebi.ac.uk/pdbsum/7chv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7chv ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=FZX:1-(phenylmethyl)imidazole-2-carboxylic+acid'>FZX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaVIM-2, bla vim-2, bla-VIM-2, blasVIM-2, blaVIM2, blm, VIM-2, vim-2, PAERUG_P32_London_17_VIM_2_10_11_06255 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=7chv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7chv OCA], [https://pdbe.org/7chv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7chv RCSB], [https://www.ebi.ac.uk/pdbsum/7chv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7chv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (i.e., most important pharmacophore features) steered molecular fitting and virtual screening. Comparative analyses of numerous protein-ligand complexes using AncPhore revealed that anchor pharmacophore features are biologically important, commonly associated with protein conservative characteristics, and have significant contributions to the binding affinity. Performance evaluation of AncPhore showed that it had substantially improved prediction ability on different types of target proteins including metalloenzymes by considering the specific contributions and diversity of anchor pharmacophore features. To demonstrate the practicability of AncPhore, we screened commercially available chemical compounds and discovered a set of structurally diverse inhibitors for clinically relevant metallo-beta-lactamases (MBLs); of them, 4 and 6 manifested potent inhibitory activity to VIM-2, NDM-1 and IMP-1 MBLs. Crystallographic analyses of VIM-2:4 complex revealed the precise inhibition mode of 4 with VIM-2, highly consistent with the defined anchor pharmacophore features. Besides, we also identified new hit compounds by using AncPhore for indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), another class of clinically relevant metalloenzymes. This work reveals anchor pharmacophore as a valuable concept for target-centered drug discovery and illustrates the potential of AncPhore to efficiently identify new inhibitors for different types of protein targets. | ||
| + | |||
| + | AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo-beta-lactamases and indoleamine/tryptophan 2,3-dioxygenases.,Dai Q, Yan Y, Ning X, Li G, Yu J, Deng J, Yang L, Li GB Acta Pharm Sin B. 2021 Jul;11(7):1931-1946. doi: 10.1016/j.apsb.2021.01.018. Epub, 2021 Jan 26. PMID:34386329<ref>PMID:34386329</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7chv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Li G | + | [[Category: Li, G B]] |
| - | [[Category: Yan Y | + | [[Category: Yan, Y H]] |
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Metallo-beta-lactamase vim-2]] | ||
| + | [[Category: Vim-2]] | ||
Revision as of 11:47, 27 April 2022
Metallo-Beta-Lactamase VIM-2 in complex with 1-benzyl-1H-imidazole-2-carboxylic acid
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