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==Pantothenate synthetase in complex with 6-methoxy-1-benzofuran-3-yl acetic acid==
==Pantothenate synthetase in complex with 6-methoxy-1-benzofuran-3-yl acetic acid==
<StructureSection load='4ddh' size='340' side='right' caption='[[4ddh]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
<StructureSection load='4ddh' size='340' side='right'caption='[[4ddh]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ddh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DDH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DDH FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ddh]] 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=4DDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DDH FirstGlance]. <br>
</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=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MS0:(6-METHOXY-1-BENZOFURAN-3-YL)ACETIC+ACID'>MS0</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.07&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ddk|4ddk]], [[4ddm|4ddm]]</td></tr>
<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=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MS0:(6-METHOXY-1-BENZOFURAN-3-YL)ACETIC+ACID'>MS0</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MT3707, MTCY07H7B.20, panC, Rv3602c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4ddh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ddh OCA], [https://pdbe.org/4ddh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ddh RCSB], [https://www.ebi.ac.uk/pdbsum/4ddh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ddh ProSAT]</span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] </span></td></tr>
<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=4ddh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ddh OCA], [http://pdbe.org/4ddh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ddh RCSB], [http://www.ebi.ac.uk/pdbsum/4ddh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ddh ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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> 
[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;">
== Publication Abstract from PubMed ==
In 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<ref>PMID:23872845</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ddh" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Pantoate--beta-alanine ligase]]
[[Category: Large Structures]]
[[Category: Silvestre, H L]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Alpha beta/adenine nucleotide alpha hydrolase-like]]
[[Category: Silvestre HL]]
[[Category: Fragment-based drug discovery]]
[[Category: Ligase-ligase inhibitor complex]]
[[Category: Pantoate and b-ala binding]]

Latest revision as of 17:32, 14 March 2024

Pantothenate synthetase in complex with 6-methoxy-1-benzofuran-3-yl acetic acidPantothenate synthetase in complex with 6-methoxy-1-benzofuran-3-yl acetic acid

Structural highlights

4ddh is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.07Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PANC_MYCTU Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.[1]

See Also

References

  1. ↑ Zheng R, Blanchard JS. Steady-state and pre-steady-state kinetic analysis of Mycobacterium tuberculosis pantothenate synthetase. Biochemistry. 2001 Oct 30;40(43):12904-12. PMID:11669627

4ddh, resolution 2.07Å

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