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| | <StructureSection load='3a4h' size='340' side='right'caption='[[3a4h]], [[Resolution|resolution]] 3.06Å' scene=''> | | <StructureSection load='3a4h' size='340' side='right'caption='[[3a4h]], [[Resolution|resolution]] 3.06Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3a4h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"streptomyces_autotrophicus"_takamiya_and_tubaki_1956 "streptomyces autotrophicus" takamiya and tubaki 1956]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A4H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3a4h]] 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=3A4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A4H FirstGlance]. <br> |
| - | </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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 3.06Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3a4g|3a4g]], [[3a4z|3a4z]], [[3a50|3a50]], [[3a51|3a51]]</div></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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vdh ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2074 "Streptomyces autotrophicus" Takamiya and Tubaki 1956])</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=3a4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a4h OCA], [https://pdbe.org/3a4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a4h RCSB], [https://www.ebi.ac.uk/pdbsum/3a4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a4h 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=3a4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a4h OCA], [https://pdbe.org/3a4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a4h RCSB], [https://www.ebi.ac.uk/pdbsum/3a4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a4h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CPVDH_PSEAH CPVDH_PSEAH] |
| | == 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: Streptomyces autotrophicus takamiya and tubaki 1956]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arisawa, A]] | + | [[Category: Pseudonocardia autotrophica]] |
| - | [[Category: Cheon, W K]] | + | [[Category: Arisawa A]] |
| - | [[Category: Fujii, Y]] | + | [[Category: Cheon WK]] |
| - | [[Category: Tamura, T]] | + | [[Category: Fujii Y]] |
| - | [[Category: Yasutake, Y]] | + | [[Category: Tamura T]] |
| - | [[Category: Cytochrome p450]]
| + | [[Category: Yasutake Y]] |
| - | [[Category: Hemoprotein]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Vitamin d3 hydroxylase]]
| + | |
| Structural highlights
Function
CPVDH_PSEAH
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Vitamin D(3) hydroxylase (Vdh) isolated from actinomycete Pseudonocardia autotrophica is a cytochrome P450 (CYP) responsible for the biocatalytic conversion of vitamin D(3) (VD(3)) to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)VD(3)) by P. autotrophica. Although its biological function is unclear, Vdh is capable of catalyzing the two-step hydroxylation of VD(3), i.e. the conversion of VD(3) to 25-hydroxyvitamin D(3) (25(OH)VD(3)) and then of 25(OH)VD(3) to 1alpha,25(OH)(2)VD(3), a hormonal form of VD(3). Here we describe the crystal structures of wild-type Vdh (Vdh-WT) in the substrate-free form and of the highly active quadruple mutant (Vdh-K1) generated by directed evolution in the substrate-free, VD(3)-bound, and 25(OH)VD(3)-bound forms. Vdh-WT exhibits an open conformation with the distal heme pocket exposed to the solvent both in the presence and absence of a substrate, whereas Vdh-K1 exhibits a closed conformation in both the substrate-free and substrate-bound forms. The results suggest that the conformational equilibrium was largely shifted toward the closed conformation by four amino acid substitutions scattered throughout the molecule. The substrate-bound structure of Vdh-K1 accommodates both VD(3) and 25(OH)VD(3) but in an anti-parallel orientation. The occurrence of the two secosteroid binding modes accounts for the regioselective sequential VD(3) hydroxylation activities. Moreover, these structures determined before and after directed evolution, together with biochemical and spectroscopic data, provide insights into how directed evolution has worked for significant enhancement of both the VD(3) 25-hydroxylase and 25(OH)VD(3) 1alpha-hydroxylase activities.
Structural evidence for enhancement of sequential vitamin D3 hydroxylation activities by directed evolution of cytochrome P450 vitamin D3 hydroxylase.,Yasutake Y, Fujii Y, Nishioka T, Cheon WK, Arisawa A, Tamura T J Biol Chem. 2010 Oct 8;285(41):31193-201. Epub 2010 Jul 27. PMID:20667833[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yasutake Y, Fujii Y, Nishioka T, Cheon WK, Arisawa A, Tamura T. Structural evidence for enhancement of sequential vitamin D3 hydroxylation activities by directed evolution of cytochrome P450 vitamin D3 hydroxylase. J Biol Chem. 2010 Oct 8;285(41):31193-201. Epub 2010 Jul 27. PMID:20667833 doi:10.1074/jbc.M110.147009
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