3fcq: Difference between revisions
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==Thermolysin inhibition== | ==Thermolysin inhibition== | ||
<StructureSection load='3fcq' size='340' side='right' caption='[[3fcq]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='3fcq' size='340' side='right'caption='[[3fcq]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3fcq]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3fcq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_thermoproteolyticus Bacillus thermoproteolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FCQ FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=M3S:2-(ACETYLOXY)-3-METHYLBENZOIC+ACID'>M3S</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=3fcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fcq OCA], [https://pdbe.org/3fcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fcq RCSB], [https://www.ebi.ac.uk/pdbsum/3fcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fcq ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/THER_BACTH THER_BACTH] Extracellular zinc metalloprotease. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fcq_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fcq_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 31: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[Thermolysin|Thermolysin]] | *[[Thermolysin 3D structures|Thermolysin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 37: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus thermoproteolyticus]] | [[Category: Bacillus thermoproteolyticus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Englert | [[Category: Englert L]] | ||
[[Category: Heine | [[Category: Heine A]] | ||
[[Category: Klebe | [[Category: Klebe G]] | ||
[[Category: Silber | [[Category: Silber K]] | ||
[[Category: Steuber | [[Category: Steuber H]] | ||
Latest revision as of 09:44, 6 September 2023
Thermolysin inhibitionThermolysin inhibition
Structural highlights
FunctionTHER_BACTH Extracellular zinc metalloprotease. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFragment-based drug discovery has gained a foothold in today's lead identification processes. We present the application of in silico fragment-based screening for the discovery of novel lead compounds for the metalloendoproteinase thermolysin. We have chosen thermolysin to validate our screening approach as it is a well-studied enzyme and serves as a model system for other proteases. A protein-targeted virtual library was designed and screening was carried out using the program AutoDock. Two fragment hits could be identified. For one of them, the crystal structure in complex with thermolysin is presented. This compound was selected for structure-based optimization of binding affinity and improvement of ligand efficiency, while concomitantly keeping the fragment-like properties of the initial hit. Redesigning the zinc coordination group revealed a novel class of fragments possessing K(i) values as low as 128 muM, thus they provide a good starting point for further hit evolution in a tailored lead design. Fragment-Based Lead Discovery: Screening and Optimizing Fragments for Thermolysin Inhibition.,Englert L, Silber K, Steuber H, Brass S, Over B, Gerber HD, Heine A, Diederich WE, Klebe G ChemMedChem. 2010 Apr 14. PMID:20394106[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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