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==Crystal structure of cytochrome P450 CYP267B1 from Sorangium cellulosum So ce56== | |||
<StructureSection load='6gk5' size='340' side='right' caption='[[6gk5]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6gk5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GK5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GK5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gk5 OCA], [http://pdbe.org/6gk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gk5 RCSB], [http://www.ebi.ac.uk/pdbsum/6gk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gk5 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Oxidative biocatalytic reactions performed by cytochrome P450 enzymes (P450s) are of high interest for the chemical and pharmaceutical industries. CYP267B1 is a P450 enzyme from myxobacterium Sorangium cellulosum So ce56 displaying a broad substrate scope. In this work, a search for new substrates was performed, combined with product characterization, and a structural analysis of substrate-bound complexes using X-ray crystallography and computational docking. The results demonstrate the ability of CYP267B1 to perform in-chain hydroxylations of medium-chain saturated fatty acids (decanoic acid, dodecanoic acid and tetradecanoic acid) and a regioselective hydroxylation of flavanone. The fatty acids are mono-hydroxylated at different in-chain positions, with decanoic acid displaying the highest regioselectivity towards omega-3 hydroxylation. Flavanone is preferably oxidized to 3-hydroxyflavanone. High-resolution crystal structures of CYP267B1 revealed a very spacious active site pocket, similarly to other P450s able to convert macrocyclic compounds. The pocket becomes more constricted near to the heme, and is closed off from solvent by residues of the FG helices and the B-C loop. The crystal structure of the tetradecanoic acid-bound complex displays the fatty acid bound near to the heme, but in a non-productive conformation. Molecular docking allowed modeling of the productive binding modes for the four investigated fatty acids and flavanone, as well as of two substrates identified in a previous study (diclofenac and ibuprofen), explaining the observed product profiles. The obtained structures of CYP267B1 thus serve as a valuable prediction tool for substrate hydroxylations by this highly versatile enzyme and will encourage future selectivity changes by rational protein engineering. | |||
Structural insights into oxidation of medium-chain fatty acids and flavanone by myxobacterial cytochrome P450 CYP267B1.,Jozwik IK, Litzenburger M, Khatri Y, Schifrin A, Girhard M, Urlacher V, Thunnissen AWH, Bernhardt R Biochem J. 2018 Jul 25. pii: BCJ20180402. doi: 10.1042/BCJ20180402. PMID:30045877<ref>PMID:30045877</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6gk5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Jozwik, I K]] | |||
[[Category: Thunnissen, A M.W H]] | |||
[[Category: Bacterial protein]] | |||
[[Category: Biocatalysis]] | |||
[[Category: Cytochrome p-450 enzyme system]] | |||
[[Category: Cytochrome p450]] | |||
[[Category: Flavanone]] | |||
[[Category: Heme]] | |||
[[Category: Hydroxylation]] | |||
[[Category: Myristic acid]] | |||
[[Category: Oxidation-reduction]] | |||
[[Category: Oxidoreductase]] | |||
[[Category: Sorangium cellulosum]] | |||
[[Category: Tetradecanoic acid]] | |||
Revision as of 00:57, 10 August 2018
Crystal structure of cytochrome P450 CYP267B1 from Sorangium cellulosum So ce56Crystal structure of cytochrome P450 CYP267B1 from Sorangium cellulosum So ce56
Structural highlights
Publication Abstract from PubMedOxidative biocatalytic reactions performed by cytochrome P450 enzymes (P450s) are of high interest for the chemical and pharmaceutical industries. CYP267B1 is a P450 enzyme from myxobacterium Sorangium cellulosum So ce56 displaying a broad substrate scope. In this work, a search for new substrates was performed, combined with product characterization, and a structural analysis of substrate-bound complexes using X-ray crystallography and computational docking. The results demonstrate the ability of CYP267B1 to perform in-chain hydroxylations of medium-chain saturated fatty acids (decanoic acid, dodecanoic acid and tetradecanoic acid) and a regioselective hydroxylation of flavanone. The fatty acids are mono-hydroxylated at different in-chain positions, with decanoic acid displaying the highest regioselectivity towards omega-3 hydroxylation. Flavanone is preferably oxidized to 3-hydroxyflavanone. High-resolution crystal structures of CYP267B1 revealed a very spacious active site pocket, similarly to other P450s able to convert macrocyclic compounds. The pocket becomes more constricted near to the heme, and is closed off from solvent by residues of the FG helices and the B-C loop. The crystal structure of the tetradecanoic acid-bound complex displays the fatty acid bound near to the heme, but in a non-productive conformation. Molecular docking allowed modeling of the productive binding modes for the four investigated fatty acids and flavanone, as well as of two substrates identified in a previous study (diclofenac and ibuprofen), explaining the observed product profiles. The obtained structures of CYP267B1 thus serve as a valuable prediction tool for substrate hydroxylations by this highly versatile enzyme and will encourage future selectivity changes by rational protein engineering. Structural insights into oxidation of medium-chain fatty acids and flavanone by myxobacterial cytochrome P450 CYP267B1.,Jozwik IK, Litzenburger M, Khatri Y, Schifrin A, Girhard M, Urlacher V, Thunnissen AWH, Bernhardt R Biochem J. 2018 Jul 25. pii: BCJ20180402. doi: 10.1042/BCJ20180402. PMID:30045877[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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