3c6g

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{{STRUCTURE_3c6g| PDB=3c6g | SCENE= }}
 
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===Crystal structure of CYP2R1 in complex with vitamin D3===
 
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{{ABSTRACT_PUBMED_18511070}}
 
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==Disease==
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==Crystal structure of CYP2R1 in complex with vitamin D3==
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[[http://www.uniprot.org/uniprot/CP2R1_HUMAN CP2R1_HUMAN]] Defects in CYP2R1 are the cause of rickets vitamin D-dependent type 1B (VDDR1B) [MIM:[http://omim.org/entry/600081 600081]]; also known as pseudovitamin D(3) deficiency rickets due to 25-hydroxylase deficiency. A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activityand low levels of 25-hydroxyvitamin D.<ref>PMID:15128933</ref>
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<StructureSection load='3c6g' size='340' side='right'caption='[[3c6g]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3c6g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ojd 2ojd]. The November 2012 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Vitamin D Receptor'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2012_11 10.2210/rcsb_pdb/mom_2012_11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6G FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PRD_900012:beta-cyclodextrin'>PRD_900012</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=VD3:(1S,3Z)-3-[(2E)-2-[(1R,3AR,7AS)-7A-METHYL-1-[(2R)-6-METHYLHEPTAN-2-YL]-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-4-METHYLIDENE-CYCLOHEXAN-1-OL'>VD3</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6g OCA], [https://pdbe.org/3c6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c6g RCSB], [https://www.ebi.ac.uk/pdbsum/3c6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c6g ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CP2R1_HUMAN CP2R1_HUMAN] Defects in CYP2R1 are the cause of rickets vitamin D-dependent type 1B (VDDR1B) [MIM:[https://omim.org/entry/600081 600081]; also known as pseudovitamin D(3) deficiency rickets due to 25-hydroxylase deficiency. A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activityand low levels of 25-hydroxyvitamin D.<ref>PMID:15128933</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CP2R1_HUMAN CP2R1_HUMAN] Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D(2) and D(3).<ref>PMID:12867411</ref> <ref>PMID:15465040</ref> <ref>PMID:18511070</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/3c6g_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3c6g ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. CYP2R1 catalyzes the initial step converting vitamin D into 25-hydroxyvitamin D. A CYP2R1 gene mutation causes an inherited form of rickets due to 25-hydroxylase deficiency. To understand the narrow substrate specificity of CYP2R1 we obtained the hemeprotein in a highly purified state, confirmed the enzyme as a vitamin D 25-hydroxylase, and solved the crystal structure of CYP2R1 in complex with vitamin D3. The CYP2R1 structure adopts a closed conformation with the substrate access channel being covered by the ordered B'-helix and slightly opened to the surface, which defines the substrate entrance point. The active site is lined by conserved, mostly hydrophobic residues. Vitamin D3 is bound in an elongated conformation with the aliphatic side-chain pointing toward the heme. The structure reveals the secosteroid binding mode in an extended active site and allows rationalization of the molecular basis of the inherited rickets associated with CYP2R1.
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==Function==
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Structural analysis of CYP2R1 in complex with vitamin D3.,Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW J Mol Biol. 2008 Jun 27;380(1):95-106. Epub 2008 Apr 8. PMID:18511070<ref>PMID:18511070</ref>
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[[http://www.uniprot.org/uniprot/CP2R1_HUMAN CP2R1_HUMAN]] Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D(2) and D(3).<ref>PMID:12867411</ref><ref>PMID:15465040</ref><ref>PMID:18511070</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3c6g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ojd 2ojd]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6G OCA].
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</div>
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<div class="pdbe-citations 3c6g" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Cytochrome P450|Cytochrome P450]]
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018511070</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Large Structures]]
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[[Category: Bochkarev, A.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Edwards, A M.]]
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[[Category: Vitamin D Receptor]]
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[[Category: Loppnau, P.]]
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[[Category: Arrowsmith CH]]
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[[Category: Min, J.]]
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[[Category: Bochkarev A]]
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[[Category: Park, H.]]
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[[Category: Edwards AM]]
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[[Category: Plotnikov, A N.]]
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[[Category: Loppnau P]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Min J]]
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[[Category: Strushkevich, N V.]]
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[[Category: Park H]]
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[[Category: Sundstrom, M.]]
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[[Category: Plotnikov AN]]
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[[Category: Tempel, W.]]
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[[Category: Strushkevich NV]]
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[[Category: Weigelt, J.]]
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[[Category: Sundstrom M]]
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[[Category: Cytochrome p450]]
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[[Category: Tempel W]]
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[[Category: Disease mutation]]
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[[Category: Weigelt J]]
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[[Category: Drug metabolism]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Heme]]
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[[Category: Iron]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Microsome]]
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[[Category: Monooxygenase]]
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[[Category: Oxidoreductase]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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[[Category: Vitamin d 25-hydroxylase]]
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[[Category: Vitamin d3]]
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Current revision

Crystal structure of CYP2R1 in complex with vitamin D3

PDB ID 3c6g

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