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| | ==Zebra Fish CYP-450 17A1 Mutant Abiraterone Complex== | | ==Zebra Fish CYP-450 17A1 Mutant Abiraterone Complex== |
| - | <StructureSection load='6b82' size='340' side='right' caption='[[6b82]], [[Resolution|resolution]] 3.03Å' scene=''> | + | <StructureSection load='6b82' size='340' side='right'caption='[[6b82]], [[Resolution|resolution]] 3.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b82]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B82 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B82 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b82]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B82 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AER:ABIRATERONE'>AER</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 3.03Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cyp17a1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AER:ABIRATERONE'>AER</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b82 OCA], [http://pdbe.org/6b82 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b82 RCSB], [http://www.ebi.ac.uk/pdbsum/6b82 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b82 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=6b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b82 OCA], [https://pdbe.org/6b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b82 RCSB], [https://www.ebi.ac.uk/pdbsum/6b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b82 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A8M1PIC7_DANRE A0A8M1PIC7_DANRE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6b82" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6b82" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Egli, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Pallan, P S]] | + | [[Category: Egli M]] |
| - | [[Category: 17a-hydroxylase]] | + | [[Category: Pallan PS]] |
| - | [[Category: 17a-hydroxylation]]
| + | |
| - | [[Category: Abiraterone]]
| + | |
| - | [[Category: Cyp17a1 mutant]]
| + | |
| - | [[Category: Cytochrome p450]]
| + | |
| - | [[Category: Cytochrome p450 oxidoreductase]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Heme protein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Microsome]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: P450 17a1]]
| + | |
| Structural highlights
Function
A0A8M1PIC7_DANRE
Publication Abstract from PubMed
Cytochrome P450 (P450) 17A1 catalyzes the oxidations of progesterone and pregnenolone and is the major source of androgens. The enzyme catalyzes both 17alpha-hydroxylation and a subsequent 17alpha, 20-lyase reaction, and several mechanisms have been proposed for the latter step. Zebrafish P450 17A2 catalyzes only the 17alpha-hydroxylations. We previously reported high similarity of the crystal structures of zebrafish P450 17A1 and 17A2 and human P450 17A1 (Pallan et al. (2015) J. Biol. Chem. 290, 3248- 3268). Five residues near the heme, which differed, were changed. We also crystallized this five-residue zebrafish P450 17A1 mutant, and the active site still resembled the structure in the other proteins, with some important differences. These P450 17A1 and 17A2 mutants had catalytic profiles more similar to each other than did the wild-type proteins. Docking with these structures can explain several minor products, which require multiple enzyme conformations. The 17alpha-hydroperoxy (OOH) derivatives of the steroids were used as oxygen surrogates. Human P450 17A1 and zebrafish P450s 17A1 and P450 17A2 readily converted these to the lyase products in the absence of other proteins or cofactors (with catalytically competent kinetics), plus hydroxylated 17alpha-hydroxy steroids. The 17alpha-OOH results indicate that a "Compound I" (FeO(3+)) intermediate is capable of formation and can be used to rationalize the products. We conclude that zebrafish P450 17A2 is capable of lyase activity with the 17alpha-OOH steroids because it can achieve an appropriate conformation for lyase catalysis in this system that is precluded in the conventional reaction.
Inherent steroid 17alpha,20-lyase activity in defunct cytochrome P450 17A enzymes.,Gonzalez E, Johnson KM, Pallan PS, Phan TTN, Zhang W, Lei LI, Wawrzak Z, Yoshimoto FK, Egli M, Guengerich FP J Biol Chem. 2017 Dec 6. pii: RA117.000504. doi: 10.1074/jbc.RA117.000504. PMID:29212707[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gonzalez E, Johnson KM, Pallan PS, Phan TTN, Zhang W, Lei LI, Wawrzak Z, Yoshimoto FK, Egli M, Guengerich FP. Inherent steroid 17alpha,20-lyase activity in defunct cytochrome P450 17A enzymes. J Biol Chem. 2017 Dec 6. pii: RA117.000504. doi: 10.1074/jbc.RA117.000504. PMID:29212707 doi:http://dx.doi.org/10.1074/jbc.RA117.000504
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