3dl9: Difference between revisions

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<StructureSection load='3dl9' size='340' side='right'caption='[[3dl9]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
<StructureSection load='3dl9' size='340' side='right'caption='[[3dl9]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3dl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DL9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3dl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DL9 FirstGlance]. <br>
</td></tr><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=V2H:(1S,3R,5Z,7E,22E)-9,10-SECOERGOSTA-5,7,10,22-TETRAENE-1,3-DIOL'>V2H</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.721&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3czh|3czh]]</div></td></tr>
<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=V2H:(1S,3R,5Z,7E,22E)-9,10-SECOERGOSTA-5,7,10,22-TETRAENE-1,3-DIOL'>V2H</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2R1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3dl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dl9 OCA], [https://pdbe.org/3dl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dl9 RCSB], [https://www.ebi.ac.uk/pdbsum/3dl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dl9 ProSAT]</span></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=3dl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dl9 OCA], [https://pdbe.org/3dl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dl9 RCSB], [https://www.ebi.ac.uk/pdbsum/3dl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dl9 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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>
[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>  
== Function ==
== Function ==
[[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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Bochkarev, A]]
[[Category: Bochkarev A]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Gilep, A A]]
[[Category: Gilep AA]]
[[Category: Loppnau, P]]
[[Category: Loppnau P]]
[[Category: Park, H]]
[[Category: Park H]]
[[Category: Structural genomic]]
[[Category: Strushkevich NV]]
[[Category: Strushkevich, N V]]
[[Category: Tempel W]]
[[Category: Tempel, W]]
[[Category: Wilkstrom M]]
[[Category: Wilkstrom, M]]
[[Category: Cytochrome p450]]
[[Category: Disease mutation]]
[[Category: Drug metabolism]]
[[Category: Endoplasmic reticulum]]
[[Category: Heme]]
[[Category: Iron]]
[[Category: Membrane]]
[[Category: Metal-binding]]
[[Category: Microsome]]
[[Category: Monooxygenase]]
[[Category: Oxidoreductase]]
[[Category: Sgc]]
[[Category: Vitamin d]]
[[Category: Vitamin s 25-hydroxylase]]

Latest revision as of 15:48, 30 August 2023

Crystal structure of CYP2R1 in complex with 1-alpha-hydroxy-vitamin D2Crystal structure of CYP2R1 in complex with 1-alpha-hydroxy-vitamin D2

Structural highlights

3dl9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.721Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CP2R1_HUMAN Defects in CYP2R1 are the cause of rickets vitamin D-dependent type 1B (VDDR1B) [MIM: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.[1]

Function

CP2R1_HUMAN Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D(2) and D(3).[2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7711-5. Epub 2004 May 5. PMID:15128933 doi:10.1073/pnas.0402490101
  2. ↑ Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003 Sep 26;278(39):38084-93. Epub 2003 Jul 16. PMID:12867411 doi:10.1074/jbc.M307028200
  3. ↑ Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun. 2004 Nov 5;324(1):451-7. PMID:15465040 doi:S0006-291X(04)02115-1
  4. ↑ Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008 Jun 27;380(1):95-106. Epub 2008 Apr 8. PMID:18511070 doi:10.1016/j.jmb.2008.03.065

3dl9, resolution 2.72Å

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