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| | <StructureSection load='3ojw' size='340' side='right'caption='[[3ojw]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3ojw' size='340' side='right'caption='[[3ojw]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ojw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OJW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ojw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OJW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ojx|3ojx]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYPOR, Por ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NADPH--hemoprotein_reductase NADPH--hemoprotein reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.2.4 1.6.2.4] </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=3ojw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ojw OCA], [https://pdbe.org/3ojw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ojw RCSB], [https://www.ebi.ac.uk/pdbsum/3ojw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ojw 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=3ojw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ojw OCA], [https://pdbe.org/3ojw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ojw RCSB], [https://www.ebi.ac.uk/pdbsum/3ojw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ojw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NCPR_RAT NCPR_RAT]] This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
| + | [https://www.uniprot.org/uniprot/NCPR_RAT NCPR_RAT] This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: NADPH--hemoprotein reductase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Choi, V]] | + | [[Category: Choi V]] |
| - | [[Category: Hamdane, D]] | + | [[Category: Hamdane D]] |
| - | [[Category: Im, S C]] | + | [[Category: Im S-C]] |
| - | [[Category: Kasper, C]] | + | [[Category: Kasper C]] |
| - | [[Category: Kim, J J.P]] | + | [[Category: Kim J-JP]] |
| - | [[Category: Shen, A]] | + | [[Category: Shen A]] |
| - | [[Category: Waskell, L]] | + | [[Category: Waskell L]] |
| - | [[Category: Xia, C]] | + | [[Category: Xia C]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Cypor]]
| + | |
| - | [[Category: Cytochrome p450 reductase]]
| + | |
| - | [[Category: Disulfide crosslinked]]
| + | |
| - | [[Category: Inactive]]
| + | |
| - | [[Category: Nadp+ free]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
NCPR_RAT This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Publication Abstract from PubMed
The crystal structure of NADPH-cytochrome P450 reductase (CYPOR) implies that a large domain movement is essential for electron transfer from NADPH via FAD and FMN to its redox partners. To test this hypothesis, a disulfide bond was engineered between residues Asp(147) and Arg(514) in the FMN and FAD domains, respectively. The cross-linked form of this mutant protein, designated 147CC514, exhibited a significant decrease in the rate of interflavin electron transfer and large (>/=90%) decreases in rates of electron transfer to its redox partners, cytochrome c and cytochrome P450 2B4. Reduction of the disulfide bond restored the ability of the mutant to reduce its redox partners, demonstrating that a conformational change is essential for CYPOR function. The crystal structures of the mutant without and with NADP(+) revealed that the two flavin domains are joined by a disulfide linkage and that the relative orientations of the two flavin rings are twisted approximately 20 degrees compared with the wild type, decreasing the surface contact area between the two flavin rings. Comparison of the structures without and with NADP(+) shows movement of the Gly(631)-Asn(635) loop. In the NADP(+)-free structure, the loop adopts a conformation that sterically hinders NADP(H) binding. The structure with NADP(+) shows movement of the Gly(631)-Asn(635) loop to a position that permits NADP(H) binding. Furthermore, comparison of these mutant and wild type structures strongly suggests that the Gly(631)-Asn(635) loop movement controls NADPH binding and NADP(+) release; this loop movement in turn facilitates the flavin domain movement, allowing electron transfer from FMN to the CYPOR redox partners.
Conformational Changes of NADPH-Cytochrome P450 Oxidoreductase Are Essential for Catalysis and Cofactor Binding.,Xia C, Hamdane D, Shen AL, Choi V, Kasper CB, Pearl NM, Zhang H, Im SC, Waskell L, Kim JJ J Biol Chem. 2011 May 6;286(18):16246-60. Epub 2011 Feb 23. PMID:21345800[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xia C, Hamdane D, Shen AL, Choi V, Kasper CB, Pearl NM, Zhang H, Im SC, Waskell L, Kim JJ. Conformational Changes of NADPH-Cytochrome P450 Oxidoreductase Are Essential for Catalysis and Cofactor Binding. J Biol Chem. 2011 May 6;286(18):16246-60. Epub 2011 Feb 23. PMID:21345800 doi:10.1074/jbc.M111.230532
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