View source for 6oyu


==Structure of an ancestral-reconstructed cytochrome P450 1B1 with alpha-naphthoflavone==
<StructureSection load='6oyu' size='340' side='right'caption='[[6oyu]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6oyu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OYU 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]] 2.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BHF:2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE'>BHF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6oyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oyu OCA], [https://pdbe.org/6oyu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oyu RCSB], [https://www.ebi.ac.uk/pdbsum/6oyu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oyu ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable with T50 values ~30-40 degrees C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared to related extant forms, but also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. While extant human CYP1B1 has one molecule of alpha-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17beta-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to their thermostability.

Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability.,Bart AG, Harris KL, Gillam EMJ, Scott EE J Biol Chem. 2020 Mar 10. pii: RA119.010727. doi: 10.1074/jbc.RA119.010727. PMID:32156703<ref>PMID:32156703</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6oyu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bart AG]]
[[Category: Harris KL]]
[[Category: Scott EE]]