OCA at 09:46, 25 October 2023

OCA — Wed, 25 Oct 2023 09:46:37 GMT

←Older revision		Revision as of 09:46, 25 October 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 7tnf is ~~ON HOLD until Paper~~ Publication	+	==The crystal structure of F298V CYP199A4 bound to 4-phenylbenzoic acid==
		+	<StructureSection load='7tnf' size='340' side='right'caption='[[7tnf]], [[Resolution\|resolution]] 1.54Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7tnf]] 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=7TNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNF 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]] 1.539Å</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Z7Z:biphenyl-4-carboxylic+acid'>Z7Z</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=7tnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnf OCA], [https://pdbe.org/7tnf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnf RCSB], [https://www.ebi.ac.uk/pdbsum/7tnf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnf ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q2IU02_RHOP2 Q2IU02_RHOP2]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The cytochrome P450 (CYP) family of heme monooxygenases catalyse the selective oxidation of C-H bonds under ambient conditions. The CYP199A4 enzyme from Rhodopseudomonas palustris catalyses aliphatic oxidation of 4-cyclohexylbenzoic acid but not the aromatic oxidation of 4-phenylbenzoic acid, due to the distinct mechanisms of aliphatic and aromatic oxidation. The aromatic substrates 4-benzyl-, 4-phenoxy- and 4-benzoyl-benzoic acid and methoxy-substituted phenylbenzoic acids were assessed to see if they could achieve an orientation more amenable to aromatic oxidation. CYP199A4 could catalyse the efficient benzylic oxidation of 4-benzylbenzoic acid. The methoxy-substituted phenylbenzoic acids were oxidatively demethylated with low activity. However, no aromatic oxidation was observed with any of these substrates. Crystal structures of CYP199A4 with 4-(3'-methoxyphenyl)benzoic acid demonstrated that the substrate binding mode was like that of 4-phenylbenzoic acid. 4-Phenoxy- and 4-benzoyl-benzoic acid bound with the ether or ketone oxygen atom hydrogen-bonded to the heme aqua ligand. We also investigated whether the substitution of phenylalanine residues in the active site could permit aromatic hydroxylation. Mutagenesis of the F298 residue to a valine did not significantly alter the substrate binding position or enable the aromatic oxidation of 4-phenylbenzoic acid; however the F182L mutant was able to catalyse 4-phenylbenzoic acid oxidation generating 2'-hydroxy-, 3'-hydroxy- and 4'-hydroxy metabolites in a 83 : 9 : 8 ratio, respectively. Molecular dynamics simulations, in which the distance and angle of attack were considered, demonstrated that in the F182L variant, in contrast to the wild-type enzyme, the phenyl ring of 4-phenylbenzoic acid attained a productive geometry for aromatic oxidation to occur.

-	~~Authors:~~ Podgorski, M., ~~Bell~~, S.G.	+	Enabling Aromatic Hydroxylation in a Cytochrome P450 Monooxygenase Enzyme through Protein Engineering.,Coleman T, Lee JZH, Kirk AM, Doherty DZ, Podgorski MN, Pinidiya DK, Bruning JB, De Voss JJ, Krenske EH, Bell SG Chemistry. 2022 Dec 1;28(67):e202201895. doi: 10.1002/chem.202201895. Epub 2022 , Oct 6. PMID:36043399<ref>PMID:36043399</ref>

-	~~Description: The crystal structure~~ of ~~F298V CYP199A4 bound to 4~~-~~phenylbenzoic acid~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Podgorski, M~~]]	+	<div class="pdbe-citations 7tnf" style="background-color:#fffaf0;"></div>
-	[[Category: Bell~~, S.G~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Rhodopseudomonas palustris HaA2]]
		+	[[Category: Bell SG]]
		+	[[Category: Podgorski M]]

OCA at 06:31, 23 February 2022

OCA — Wed, 23 Feb 2022 06:31:06 GMT

←Older revision		Revision as of 06:31, 23 February 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7tnf is ON HOLD	+	The entry 7tnf is ON HOLD until Paper Publication

	Authors: Podgorski, M., Bell, S.G.		Authors: Podgorski, M., Bell, S.G.

OCA: Protected "7tnf" [edit=sysop:move=sysop]

OCA — Thu, 27 Jan 2022 05:38:03 GMT

Protected "7tnf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:38, 27 January 2022

OCA: New page: '''Unreleased structure''' The entry 7tnf is ON HOLD Authors: Podgorski, M., Bell, S.G. Description: The crystal structure of F298V CYP199A4 bound to 4-phenylbenzoic acid [[Category: U...

OCA — Thu, 27 Jan 2022 05:38:01 GMT

New page: '''Unreleased structure''' The entry 7tnf is ON HOLD Authors: Podgorski, M., Bell, S.G. Description: The crystal structure of F298V CYP199A4 bound to 4-phenylbenzoic acid [[Category: U...

New page

'''Unreleased structure'''

The entry 7tnf is ON HOLD

Authors: Podgorski, M., Bell, S.G.

Description: The crystal structure of F298V CYP199A4 bound to 4-phenylbenzoic acid
[[Category: Unreleased Structures]]
[[Category: Podgorski, M]]
[[Category: Bell, S.G]]

7tnf - Revision history

OCA at 09:46, 25 October 2023

OCA at 06:31, 23 February 2022

OCA: Protected "7tnf" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7tnf is ON HOLD Authors: Podgorski, M., Bell, S.G. Description: The crystal structure of F298V CYP199A4 bound to 4-phenylbenzoic acid [[Category: U...