4bfv: Difference between revisions
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==Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1d) and phosphate== | ==Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1d) and phosphate== | ||
<StructureSection load='4bfv' size='340' side='right' caption='[[4bfv]], [[Resolution|resolution]] 2.29Å' scene=''> | <StructureSection load='4bfv' size='340' side='right'caption='[[4bfv]], [[Resolution|resolution]] 2.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bfv]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4bfv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BFV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZVV:N-[1-(4-METHYL-5-{[2-(2-METHYLPHENOXY)ETHYL]SULFANYL}-4H-1,2,4-TRIAZOL-3-YL)ETHYL]-2-(TRIFLUOROMETHYL)BENZAMIDE'>ZVV</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZVV:N-[1-(4-METHYL-5-{[2-(2-METHYLPHENOXY)ETHYL]SULFANYL}-4H-1,2,4-TRIAZOL-3-YL)ETHYL]-2-(TRIFLUOROMETHYL)BENZAMIDE'>ZVV</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=4bfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bfv OCA], [https://pdbe.org/4bfv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bfv RCSB], [https://www.ebi.ac.uk/pdbsum/4bfv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bfv ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/COAA_MYCTU COAA_MYCTU] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 16: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4bfv" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Pantothenate kinase|Pantothenate kinase]] | *[[Pantothenate kinase 3D structures|Pantothenate kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Bergfors | [[Category: Bergfors T]] | ||
[[Category: Bjorkelid | [[Category: Bjorkelid C]] | ||
[[Category: Jones | [[Category: Jones TA]] | ||
Latest revision as of 14:50, 20 December 2023
Crystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1d) and phosphateCrystal structure of Mycobacterium tuberculosis PanK in complex with a triazole inhibitory compound (1d) and phosphate
Structural highlights
FunctionPublication Abstract from PubMedMycobacterium tuberculosis, the bacterial causative agent of tuberculosis, currently affects millions of people. The emergence of drug resistant strains makes development of new antibiotics targeting the bacterium a global health priority. Pantothenate kinase, a key enzyme in the universal biosynthesis of the essential cofactor Coenzyme A, was targeted in this study to find new tuberculosis drugs. The biochemical characterization of two new classes of compounds that inhibit pantothenate kinase from Mycobacterium tuberculosis are described, along with crystal structures of their enzyme-inhibitor complexes. These represent the first crystal structures of this enzyme with engineered inhibitors. Both classes of compounds bind in the active site of the enzyme, overlapping with the binding sites of the natural substrate and product, pantothenate and phosphopantothenate, respectively. One class of compounds also interferes with binding of the cofactor ATP. The complexes were crystallized in two crystal forms, one of which is in a new space group for this enzyme and diffracts to the highest resolution reported for any pantothenate kinase structure. These two crystal forms allowed, for the first time, modelling of the cofactor-binding loop in both open and closed conformations. The structures also show a binding-mode of ATP different from that previously reported for the Mycobacterium tuberculosis enzyme, but similar to that in the pantothenate kinases of other organisms. Structural and Biochemical Characterization of Compounds Inhibiting Mycobacterium tuberculosis PanK.,Bjorkelid C, Bergfors T, Raichurkar AK, Mukherjee K, Malolanarasimhan K, Bandodkar B, Jones TA J Biol Chem. 2013 May 10. PMID:23661699[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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