View source for 2zby


==Crystal structure of vitamin D hydroxylase cytochrome P450 105A1 (R84A mutant)==
<StructureSection load='2zby' size='340' side='right'caption='[[2zby]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2zby]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_griseolus Streptomyces griseolus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZBY 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]] 1.6&#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></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=2zby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zby OCA], [https://pdbe.org/2zby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zby RCSB], [https://www.ebi.ac.uk/pdbsum/2zby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zby ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CPXE_STRGO CPXE_STRGO] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zb/2zby_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zby ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Vitamin D 3 (VD 3), a prohormone in mammals, plays a crucial role in the maintenance of calcium and phosphorus concentrations in serum. Activation of VD 3 requires 25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney by cytochrome P450 (CYP) enzymes. Bacterial CYP105A1 converts VD 3 into 1alpha,25-dihydroxyvitamin D 3 (1alpha,25(OH) 2D 3) in two independent reactions, despite its low sequence identity with mammalian enzymes (&lt;21% identity). The present study determined the crystal structures of a highly active mutant (R84A) of CYP105A1 from Streptomyces griseolus in complex and not in complex with 1alpha,25(OH) 2D 3. The compound 1alpha,25(OH) 2D 3 is positioned 11 A from the iron atom along the I helix within the pocket. A similar binding mode is observed in the structure of the human CYP2R1-VD 3 complex, indicating a common substrate-binding mechanism for 25-hydroxylation. A comparison with the structure of wild-type CYP105A1 suggests that the loss of two hydrogen bonds in the R84A mutant increases the adaptability of the B' and F helices, creating a transient binding site. Further mutational analysis of the active site reveals that 25- and 1alpha-hydroxylations share residues that participate in these reactions. These results provide the structural basis for understanding the mechanism of the two-step hydroxylation that activates VD 3.

Crystal Structure of CYP105A1 (P450SU-1) in Complex with 1alpha,25-Dihydroxyvitamin D3(,).,Sugimoto H, Shinkyo R, Hayashi K, Yoneda S, Yamada M, Kamakura M, Ikushiro S, Shiro Y, Sakaki T Biochemistry. 2008 Apr 1;47(13):4017-27. Epub 2008 Mar 4. PMID:18314962<ref>PMID:18314962</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2zby" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces griseolus]]
[[Category: Hayashi K]]
[[Category: Ikushiro S]]
[[Category: Kamakura M]]
[[Category: Sakaki T]]
[[Category: Shinkyo R]]
[[Category: Shiro Y]]
[[Category: Sugimoto H]]
[[Category: Yamada M]]
[[Category: Yoneda S]]