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New page: '''Unreleased structure''' The entry 6m4s is ON HOLD Authors: Li, F.W., Li, S.Y. Description: Crystal Structure Analysis of the cytochrome P450 CYP-Sb21 [[Category: Unreleased Structur...
 
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'''Unreleased structure'''


The entry 6m4s is ON HOLD
==Crystal Structure Analysis of the cytochrome P450 CYP-Sb21==
<StructureSection load='6m4s' size='340' side='right'caption='[[6m4s]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M4S 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=6m4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m4s OCA], [https://pdbe.org/6m4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m4s RCSB], [https://www.ebi.ac.uk/pdbsum/6m4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m4s ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cytochrome P450 enzyme CYP-sb21 from the rare actinomycete Sebekia benihana is capable of hydroxylating the immunosuppressive drug molecule cyclosporine A (CsA) primarily at the 4th N-methyl leucine (MeLeu(4)), giving rise to gamma-hydroxy-N-methyl-l-Leu(4)-CsA (CsA-4-OH). This oxidative modification of CsA leads to dramatically reduced immunosuppressive activity while retaining the hair growth-promoting side-effect, thus demonstrating great application potential in both pharmaceutical and cosmetic industries. However, this P450 enzyme also hydroxylates CsA at the unwanted position of the 9th N-methyl leucine (MeLeu(9)), indicating that the regioselectivity needs to be improved for the development of CsA-4-OH into a commercial hair growth stimulator. Herein, we report the crystal structure of CYP-sb21 in its substrate-free form at 1.85 A. Together with sequence and 3D structure comparisons, Autodock-based substrate docking, molecular dynamics (MD) simulation, and site-directed mutagenesis, we identified a number of key residues including R294, E264, and M179 that can improve catalytic efficiency or change the regioselectivity of CYP-sb21 towards CsA, setting the stage for better enzymatic preparation of CsA-4-OH. This study also provides new insights into the substrate recognition and binding mechanism of P450 enzymes that accommodate bulky substrates.


Authors: Li, F.W., Li, S.Y.
Structure-guided manipulation of the regioselectivity of the cyclosporine A hydroxylase CYP-sb21 from Sebekia benihana.,Li F, Ma L, Zhang X, Chen J, Qi F, Huang Y, Qu Z, Yao L, Zhang W, Kim ES, Li S Synth Syst Biotechnol. 2020 Jul 28;5(3):236-243. doi:, 10.1016/j.synbio.2020.07.004. eCollection 2020 Sep. PMID:32775708<ref>PMID:32775708</ref>


Description: Crystal Structure Analysis of the cytochrome P450 CYP-Sb21
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Li, S.Y]]
<div class="pdbe-citations 6m4s" style="background-color:#fffaf0;"></div>
[[Category: Li, F.W]]
 
==See Also==
*[[Cytochrome P450 hydroxylase 3D structures|Cytochrome P450 hydroxylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Li FW]]
[[Category: Li SY]]
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