6oyv: Difference between revisions
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<StructureSection load='6oyv' size='340' side='right'caption='[[6oyv]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='6oyv' size='340' side='right'caption='[[6oyv]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6oyv]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6oyv]] 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=6OYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OYV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EST:ESTRADIOL'>EST</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></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]] 3.101Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EST:ESTRADIOL'>EST</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=6oyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oyv OCA], [https://pdbe.org/6oyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oyv RCSB], [https://www.ebi.ac.uk/pdbsum/6oyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oyv ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6oyv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6oyv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Synthetic construct | [[Category: Synthetic construct]] | ||
[[Category: Bart | [[Category: Bart AG]] | ||
[[Category: Scott | [[Category: Scott EE]] | ||
Latest revision as of 10:19, 11 October 2023
Structure of an ancestral-reconstructed cytochrome P450 1B1 with estradiolStructure of an ancestral-reconstructed cytochrome P450 1B1 with estradiol
Structural highlights
Publication Abstract from PubMedMammalian 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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