6u31: Difference between revisions

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<StructureSection load='6u31' size='340' side='right'caption='[[6u31]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
<StructureSection load='6u31' size='340' side='right'caption='[[6u31]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6u31]] 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=6U31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U31 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U31 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]] 1.578&#8491;</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]] 1.578&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PQP:4-(1H-imidazol-1-yl)benzoic+acid'>PQP</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PQP:4-(1H-imidazol-1-yl)benzoic+acid'>PQP</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=6u31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u31 OCA], [https://pdbe.org/6u31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u31 RCSB], [https://www.ebi.ac.uk/pdbsum/6u31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u31 ProSAT]</span></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=6u31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u31 OCA], [https://pdbe.org/6u31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u31 RCSB], [https://www.ebi.ac.uk/pdbsum/6u31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u31 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q2IU02_RHOP2 Q2IU02_RHOP2]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cytochrome P450 (CYP) superfamily of heme monooxygenases is involved in a range of important chemical biotransformations across nature. Azole-containing molecules have been developed as drugs that bind to the heme center of these enzymes, inhibiting their function. The optical spectrum of CYP enzymes after the addition of these inhibitors is used to assess how the molecules bind. Here we use the bacterial CYP199A4 enzyme, from Rhodopseudomonas palustris HaA2, to compare how imidazolyl and triazolyl inhibitors bind to ferric and ferrous heme. 4-(Imidazol-1-yl)benzoic acid induced a red shift in the Soret wavelength (424 nm) in the ferric enzyme along with an increase and a decrease in the intensities of the delta and alpha bands, respectively. 4-(1H-1,2,4-Triazol-1-yl)benzoic acid binds to CYP199A4 with a 10-fold lower affinity and induces a smaller red shift in the Soret band. The crystal structures of CYP199A4 with these two inhibitors confirmed that these differences in the optical spectra were due to coordination of the imidazolyl ligand to the ferric Fe, but the triazolyl inhibitor interacts with, rather than displaces, the ferric aqua ligand. Additional water molecules were present in the active site of 4-(1H-1,2,4-triazol-1-yl)benzoic acid-bound CYP199A4. The space required to accommodate these additional water molecules in the active site necessitates changes in the position of the hydrophobic phenylalanine 298 residue. Upon reduction of the heme, the imidazole-based inhibitor Fe-N ligation was not retained. A 5-coordinate heme was also the predominant species in 4-(1H-1,2,4-triazol-1-yl)benzoic acid-bound ferrous CYP199A4, but there was an obvious shoulder at 447 nm indicative of some degree of Fe-N coordination. Rather than inhibit CYP199A4, 4-(imidazol-1-yl)benzoic acid was a substrate and was oxidized to generate a metabolite derived from ring opening of the imidazolyl ring: 4-[[2-(formylamino)acetyl]amino]benzoic acid.
To Be, or Not to Be, an Inhibitor: A Comparison of Azole Interactions with and Oxidation by a Cytochrome P450 Enzyme.,Podgorski MN, Coleman T, Giang PD, Wang CR, Bruning JB, Bernhardt PV, De Voss JJ, Bell SG Inorg Chem. 2022 Jan 10;61(1):236-245. doi: 10.1021/acs.inorgchem.1c02786. Epub, 2021 Dec 15. PMID:34910500<ref>PMID:34910500</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6u31" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Rhodopseudomonas palustris HaA2]]
[[Category: Bell SG]]
[[Category: Bell SG]]
[[Category: Bruning JB]]
[[Category: Bruning JB]]
[[Category: Podgorski MN]]
[[Category: Podgorski MN]]

Latest revision as of 13:46, 13 August 2026

The crystal structure of 4-(1H-imidazol-1-yl)benzoate-bound CYP199A4

6u31, resolution 1.58Å

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