View source for 5gnl


==Cytochrome P450 Vdh (CYP107BR1) F106V mutant==
<StructureSection load='5gnl' size='340' side='right'caption='[[5gnl]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5gnl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudonocardia_autotrophica Pseudonocardia autotrophica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GNL 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</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=5gnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gnl OCA], [https://pdbe.org/5gnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gnl RCSB], [https://www.ebi.ac.uk/pdbsum/5gnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gnl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CPVDH_PSEAH CPVDH_PSEAH] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cytochromes P450 (P450s) are haem-containing enzymes that catalyze medically and industrially important oxidative reactions, and many P450s have been subjected to directed evolution and site-directed mutagenesis to improve their activity and substrate specificity. Nonetheless, in most cases the mechanism that leads to drastic changes in specific activity after the introduction of an amino-acid substitution distant from the active-site pocket is unclear. Here, two crystal structures of inactive mutants of the P450 vitamin D3 hydroxylase (Vdh), Vdh-F106V and Vdh-L348M, which were obtained in the course of protein-engineering experiments on Vdh, are reported. The overall structures of these mutants show an open conformation similar to that of wild-type Vdh (Vdh-WT), whereas a rearrangement of the common main-chain hydrogen bonds is observed in the CD-loop (residues 102-106), resulting in a more compactly folded CD-loop relative to that of Vdh-WT. The previously reported structures of Vdh-WT and of the highly active Vdh-T107A and Vdh-K1 mutants have a more stretched CD-loop, with partial formation of 310-helix-type hydrogen bonds, both in the open and closed states. Molecular-dynamics simulations also showed that the frequency of the 310-helix is significantly reduced in Vdh-F106V and Vdh-L348M. The closed conformation is crucial for substrate and ferredoxin binding to initiate the catalytic reaction of Vdh. Therefore, it is implied that the small local structural changes observed in this study might disrupt the conformational transition from the open to the closed state, thereby leading to a complete loss of vitamin D3 hydroxylase activity.

Structural insights into the mechanism of the drastic changes in enzymatic activity of the cytochrome P450 vitamin D3 hydroxylase (CYP107BR1) caused by a mutation distant from the active site.,Yasutake Y, Kameda T, Tamura T Acta Crystallogr F Struct Biol Commun. 2017 May 1;73(Pt 5):266-275. doi:, 10.1107/S2053230X17004782. Epub 2017 Apr 26. PMID:28471358<ref>PMID:28471358</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 5gnl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudonocardia autotrophica]]
[[Category: Tamura T]]
[[Category: Yasutake Y]]