7tqm
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The crystal structure of D251N CYP199A4 bound to 4-methylthiobenzoic acid== |
| + | <StructureSection load='7tqm' size='340' side='right'caption='[[7tqm]], [[Resolution|resolution]] 1.44Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7tqm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodopseudomonas_palustris_HaA2 Rhodopseudomonas palustris HaA2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQM FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.438Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4MI:4-methylsulfanylbenzoic+acid'>4MI</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=7tqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqm OCA], [https://pdbe.org/7tqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqm RCSB], [https://www.ebi.ac.uk/pdbsum/7tqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqm ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q2IU02_RHOP2 Q2IU02_RHOP2] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cytochrome P450 (CYP) heme-thiolate monooxygenases catalyze the hydroxylation of the C-H bonds of organic molecules. This reaction is initiated by a ferryl-oxo heme radical cation (Cpd I). These enzymes can also catalyze sulfoxidation reactions and the ferric-hydroperoxy complex (Cpd 0) and the Fe(III)-H(2) O(2) complex have been proposed as alternative oxidants for this transformation. To investigate this, the oxidation of 4-alkylthiobenzoic acids and 4-methoxybenzoic acid by the CYP199A4 enzyme from Rhodopseudomonas palustris HaA2 was compared using both monooxygenase and peroxygenase pathways. By examining mutants at the mechanistically important, conserved acid alcohol-pair (D251N, T252A and T252E) the relative amounts of the reactive intermediates that would form in these reactions were disturbed. Substrate binding and X-ray crystal structures helped to understand changes in the activity and enabled an attempt to evaluate whether multiple oxidants can participate in these reactions. In peroxygenase reactions the T252E mutant had higher activity towards sulfoxidation than O-demethylation but in the monooxygenase reactions with the WT enzyme the activity of both reactions was similar. The peroxygenase activity of the T252A mutant was greater for sulfoxidation reactions than the WT enzyme, which is the reverse of the activity changes observed for O-demethylation. The monooxygenase activity and coupling efficiency of sulfoxidation and oxidative demethylation were reduced by similar degrees with the T252A mutant. These observations infer that while Cpd I is required for O-dealkylation, another oxidant may contribute to sulfoxidation. Based on the activity of the CYP199A4 mutants it is proposed that this is the Fe(III)-H(2) O(2) complex which would be more abundant in the peroxide-driven reactions. | ||
| - | + | Investigating the Active Oxidants Involved in Cytochrome P450 Catalyzed Sulfoxidation Reactions.,Podgorski MN, Coleman T, Churchman LR, Bruning JB, De Voss JJ, Bell SG Chemistry. 2022 Dec 27;28(72):e202202428. doi: 10.1002/chem.202202428. Epub 2022 , Nov 9. PMID:36169207<ref>PMID:36169207</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7tqm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rhodopseudomonas palustris HaA2]] | ||
| + | [[Category: Bell SG]] | ||
| + | [[Category: Podgorski M]] | ||
Current revision
The crystal structure of D251N CYP199A4 bound to 4-methylthiobenzoic acid
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