4kf0: Difference between revisions
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==Structure of the A82F P450 BM3 heme domain== | ==Structure of the A82F P450 BM3 heme domain== | ||
<StructureSection load='4kf0' size='340' side='right' caption='[[4kf0]], [[Resolution|resolution]] 1.45Å' scene=''> | <StructureSection load='4kf0' size='340' side='right' caption='[[4kf0]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4kf0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4kf0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14581 Atcc 14581]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KF0 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> | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kew|4kew]], [[4key|4key]], [[4kf2|4kf2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kew|4kew]], [[4key|4key]], [[4kf2|4kf2]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp102A1, cyp102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp102A1, cyp102 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 ATCC 14581])</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=4kf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kf0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kf0 RCSB], [http://www.ebi.ac.uk/pdbsum/4kf0 PDBsum]</span></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=4kf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kf0 OCA], [http://pdbe.org/4kf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kf0 RCSB], [http://www.ebi.ac.uk/pdbsum/4kf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kf0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4kf0" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Atcc 14581]] | ||
[[Category: Leys, D]] | [[Category: Leys, D]] | ||
[[Category: Monooxygenase]] | [[Category: Monooxygenase]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: P450]] | [[Category: P450]] | ||
Revision as of 15:10, 4 August 2016
Structure of the A82F P450 BM3 heme domainStructure of the A82F P450 BM3 heme domain
Structural highlights
Function[CPXB_BACME] Functions as a fatty acid monooxygenase. Catalyzes hydroxylation of medium and long-chain fatty acids at omega-1, omega-2 and omega-3 positions, with optimum chain lengths of 12-16 carbons (lauric, myristic, and palmitic acids). The reductase domain is required for electron transfer from NADP to cytochrome P450. Publication Abstract from PubMedCytochrome P450 monooxygenases (P450s) have enormous potential in the production of oxychemicals, due to their unparalleled regio- and stereoselectivity. The Bacillus megaterium P450 BM3 enzyme is a key model system, with several mutants (many distant from the active site) reported to alter substrate selectivity. It has the highest reported monooxygenase activity of the P450 enzymes, and this catalytic efficiency has inspired protein engineering to enable its exploitation for biotechnologically relevant oxidations with structurally diverse substrates. However, a structural rationale is lacking to explain how these mutations have such effects in the absence of direct change to the active site architecture. Here, we provide the first crystal structures of BM3 mutants in complex with a human drug substrate, the proton pump inhibitor omeprazole. Supported by solution data, these structures reveal how mutation alters the conformational landscape and decreases the free energy barrier for transition to the substrate-bound state. Our data point to the importance of such "gatekeeper" mutations in enabling major changes in substrate recognition. We further demonstrate that these mutants catalyze the same 5-hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 enzyme. Key Mutations Alter the Cytochrome P450 BM3 Conformational Landscape and Remove Inherent Substrate Bias.,Butler CF, Peet C, Mason AE, Voice MW, Leys D, Munro AW J Biol Chem. 2013 Aug 30;288(35):25387-99. doi: 10.1074/jbc.M113.479717. Epub, 2013 Jul 3. PMID:23828198[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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