4j6b: Difference between revisions
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The | ==The 2.2 A crystal structure of CYP154C5 from Nocardia farcinica in complex with pregnenolone== | ||
<StructureSection load='4j6b' size='340' side='right'caption='[[4j6b]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4j6b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nocardia_farcinica_IFM_10152 Nocardia farcinica IFM 10152]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J6B 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PLO:(3BETA)-3-HYDROXYPREGN-5-EN-20-ONE'>PLO</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=4j6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j6b OCA], [https://pdbe.org/4j6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j6b RCSB], [https://www.ebi.ac.uk/pdbsum/4j6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j6b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5YNS8_NOCFA Q5YNS8_NOCFA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CYP154C5 from Nocardia farcinica is a bacterial cytochrome P450 monooxygenase active on steroid molecules. The enzyme has recently been shown to exhibit exclusive regioselectivity and stereoselectivity in the conversion of various pregnans and androstans, yielding 16alpha-hydroxylated steroid products. This makes the enzyme an attractive candidate for industrial application in steroid hormone synthesis. Here, crystal structures of CYP154C5 in complex with four different steroid molecules were solved at resolutions of up to 1.9 A. These are the first reported P450 structures from the CYP154 family in complex with a substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with two opposing polar regions, perfectly resembling the size and polarity distribution of the steroids and thus resulting in highly specific steroid binding with Kd values in the range 10-100 nM. Key enzyme-substrate interactions were identified that accounted for the exclusive regioselectivity and stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5-steroid structures revealed distinct structural differences, explaining the observed variations in kinetic data obtained for this P450 with the steroids pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone and nandrolone. This will facilitate the generation of variants with improved activity or altered selectivity in the future by means of protein engineering. | |||
Enzyme-substrate complex structures of CYP154C5 shed light on its mode of highly selective steroid hydroxylation.,Herzog K, Bracco P, Onoda A, Hayashi T, Hoffmann K, Schallmey A Acta Crystallogr D Biol Crystallogr. 2014 Nov;70(Pt 11):2875-89. doi:, 10.1107/S1399004714019129. Epub 2014 Oct 16. PMID:25372679<ref>PMID:25372679</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4j6b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nocardia farcinica IFM 10152]] | |||
[[Category: Herzog K]] | |||
[[Category: Hoffmann KM]] | |||