5opa: Difference between revisions
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<StructureSection load='5opa' size='340' side='right'caption='[[5opa]], [[Resolution|resolution]] 1.34Å' scene=''> | <StructureSection load='5opa' size='340' side='right'caption='[[5opa]], [[Resolution|resolution]] 1.34Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5opa]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OPA OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5opa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OPA FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2W:3-(4-fluorophenyl)-4-(imidazol-1-ylmethyl)-1-phenyl-pyrazole'>A2W</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.345Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2W:3-(4-fluorophenyl)-4-(imidazol-1-ylmethyl)-1-phenyl-pyrazole'>A2W</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5opa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5opa OCA], [https://pdbe.org/5opa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5opa RCSB], [https://www.ebi.ac.uk/pdbsum/5opa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5opa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CP121_MYCTU CP121_MYCTU] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5opa" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5opa" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis CDC1551]] | ||
[[Category: Levy | [[Category: Levy CW]] | ||
Revision as of 19:57, 13 December 2023
The crystal structure of P450 CYP121 in complex with lead compound 7bThe crystal structure of P450 CYP121 in complex with lead compound 7b
Structural highlights
FunctionPublication Abstract from PubMedThree series of biarylpyrazole imidazole and triazoles are described, which vary in the linker between the biaryl pyrazole and imidazole/triazole group. The imidazole and triazole series with the short -CH2- linker displayed promising antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC values (6.25-25 mug/mL), which was also influenced by lipophilicity. Extending the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity. The binding affinity of the compounds with CYP121A1 was determined by UV-visible optical titrations with KD values of 2.63, 35.6, and 290 muM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions observed with fluconazole and the natural substrate dicyclotyrosine. Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation.,Taban IM, Elshihawy HEAE, Torun B, Zucchini B, Williamson CJ, Altuwairigi D, Ngu AST, McLean KJ, Levy CW, Sood S, Marino LB, Munro AW, de Carvalho LPS, Simons C J Med Chem. 2017 Dec 28;60(24):10257-10267. doi: 10.1021/acs.jmedchem.7b01562., Epub 2017 Dec 7. PMID:29185746[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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