5wp2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='5wp2' size='340' side='right'caption='[[5wp2]], [[Resolution|resolution]] 1.44Å' scene=''> | <StructureSection load='5wp2' size='340' side='right'caption='[[5wp2]], [[Resolution|resolution]] 1.44Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5wp2]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5wp2]] is a 1 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=5WP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WP2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YTT:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZINE-2,5-DIONE'>YTT</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]] 1.439Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YTT:(3S,6S)-3,6-BIS(4-HYDROXYBENZYL)PIPERAZINE-2,5-DIONE'>YTT</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=5wp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wp2 OCA], [https://pdbe.org/5wp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wp2 RCSB], [https://www.ebi.ac.uk/pdbsum/5wp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wp2 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/A0A0T9WNE5_MYCTX A0A0T9WNE5_MYCTX] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5wp2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5wp2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 25: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Dornevil | [[Category: Dornevil K]] | ||
[[Category: Fielding | [[Category: Fielding A]] | ||
[[Category: Liu | [[Category: Liu A]] | ||
Latest revision as of 17:19, 4 October 2023
1.44 Angstrom crystal structure of CYP121 from Mycobacterium tuberculosis in complex with substrate and CN1.44 Angstrom crystal structure of CYP121 from Mycobacterium tuberculosis in complex with substrate and CN
Structural highlights
FunctionPublication Abstract from PubMedCYP121 is a cytochrome P450 enzyme from Mycobacterium tuberculosis that catalyzes the formation of a C-C bond between the aromatic groups of its cyclodityrosine substrate (cYY). The crystal structure of CYP121 in complex with cYY reveals that the solvent-derived ligand remains bound to the ferric ion in the enzyme-substrate complex. Whereas in the generally accepted P450 mechanism, binding of the primary substrate in the active-site triggers the release of the solvent-derived ligand, priming the metal center for reduction and subsequent O2 binding. Here we employed sodium cyanide to probe the metal-ligand exchange of the enzyme and the enzyme-substrate complex. The cyano adducts were characterized by UV-vis, EPR, and ENDOR spectroscopies and X-ray crystallography. A 100-fold increase in the affinity of cyanide binding to the enzyme-substrate complex over the ligand-free enzyme was observed. The crystal structure of the [CYP121(cYY)CN] ternary complex showed a rearrangement of the substrate in the active-site, when compared to the structure of the binary [CYP121(cYY)] complex. Transient kinetic studies showed that cYY binding resulted in a lower second-order rate constant (kon (CN)) but a much more stable cyanide adduct with 3 orders of magnitude slower koff (CN) rate. A dynamic equilibrium between multiple high- and low-spin species for both the enzyme and enzyme-substrate complex was also observed, which is sensitive to changes in both pH and temperature. Our data reveal the chemical and physical properties of the solvent-derived ligand of the enzyme, which will help to understand the initial steps of the catalytic mechanism. Probing Ligand Exchange in the P450 Enzyme CYP121 from Mycobacterium tuberculosis: Dynamic Equilibrium of the Distal Heme Ligand as a Function of pH and Temperature.,Fielding AJ, Dornevil K, Ma L, Davis I, Liu A J Am Chem Soc. 2017 Dec 6;139(48):17484-17499. doi: 10.1021/jacs.7b08911. Epub, 2017 Nov 20. PMID:29090577[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||