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==Crystal structure of pantothenate synthetase in complex with 2-(2-(4-tert-butylphenylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid== | ==Crystal structure of pantothenate synthetase in complex with 2-(2-(4-tert-butylphenylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid== | ||
<StructureSection load='4muf' size='340' side='right' caption='[[4muf]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4muf' size='340' side='right'caption='[[4muf]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4muf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUF OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4muf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUF 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]] 2.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2DJ:(2-{[(4-TERT-BUTYLPHENYL)SULFONYL]CARBAMOYL}-5-METHOXY-1H-INDOL-1-YL)ACETIC+ACID'>2DJ</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</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=4muf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muf OCA], [https://pdbe.org/4muf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4muf RCSB], [https://www.ebi.ac.uk/pdbsum/4muf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4muf ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | |||
Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery. | |||
Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.,Hung AW, Silvestre HL, Wen S, George GP, Boland J, Blundell TL, Ciulli A, Abell C ChemMedChem. 2016 Jan 5;11(1):38-42. doi: 10.1002/cmdc.201500414. Epub 2015 Oct, 21. PMID:26486566<ref>PMID:26486566</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4muf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Pantothenate synthetase|Pantothenate synthetase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: | [[Category: Blundell TL]] | ||
[[Category: | [[Category: Silvestre HL]] | ||
Latest revision as of 19:42, 20 September 2023
Crystal structure of pantothenate synthetase in complex with 2-(2-(4-tert-butylphenylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acidCrystal structure of pantothenate synthetase in complex with 2-(2-(4-tert-butylphenylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid
Structural highlights
Publication Abstract from PubMedLigand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery. Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.,Hung AW, Silvestre HL, Wen S, George GP, Boland J, Blundell TL, Ciulli A, Abell C ChemMedChem. 2016 Jan 5;11(1):38-42. doi: 10.1002/cmdc.201500414. Epub 2015 Oct, 21. PMID:26486566[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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