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==Pantothenate synthetase in complex with N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDE== | ==Pantothenate synthetase in complex with N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDE== | ||
<StructureSection load='4efk' size='340' side='right' caption='[[4efk]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='4efk' size='340' side='right'caption='[[4efk]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4efk]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4efk]] 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=4EFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EFK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0OC:N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDE'>0OC</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0OC:N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDE'>0OC</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4efk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4efk OCA], [https://pdbe.org/4efk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4efk RCSB], [https://www.ebi.ac.uk/pdbsum/4efk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4efk 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/PANC_MYCTU PANC_MYCTU]] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.<ref>PMID:11669627</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 28: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: | [[Category: Abell C]] | ||
[[Category: | [[Category: Blundell TL]] | ||
[[Category: | [[Category: Ciulli A]] | ||
[[Category: | [[Category: Silvestre HL]] | ||
Revision as of 10:09, 28 September 2022
Pantothenate synthetase in complex with N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDEPantothenate synthetase in complex with N,N-DIMETHYLTHIOPHENE-3-SULFONAMIDE
Structural highlights
Function[PANC_MYCTU] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.[1] Publication Abstract from PubMedIn fragment-based drug discovery, the weak affinities exhibited by fragments pose significant challenges for screening. Biophysical techniques are used to address this challenge, but there is no clear consensus on which cascade of methods is best suited to identify fragment hits that ultimately translate into bound X-ray structures and provide bona fide starting points for synthesis. We have benchmarked an integrated biophysical approach for fragment screening and validation against Mycobacterium tuberculosis pantothenate synthetase. A primary screen of 1,250 fragments library was performed by thermal shift, followed by secondary screen using one-dimensional NMR spectroscopy (water ligand observed gradient spectroscopy and saturation transfer difference binding experiments) and ultimate hit validation by isothermal titration calorimetry and X-ray crystallography. Our multibiophysical approach identified three distinct binding sites for fragments and laid a solid foundation for successful structure-based elaboration into potent inhibitors. Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery.,Silvestre HL, Blundell TL, Abell C, Ciulli A Proc Natl Acad Sci U S A. 2013 Jul 19. PMID:23872845[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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