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| | <StructureSection load='7l18' size='340' side='right'caption='[[7l18]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='7l18' size='340' side='right'caption='[[7l18]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7l18]] is a 2 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=7L18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L18 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7l18]] is a 2 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=7L18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L18 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>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 2.542Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Por ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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=7l18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l18 OCA], [https://pdbe.org/7l18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l18 RCSB], [https://www.ebi.ac.uk/pdbsum/7l18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l18 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=7l18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l18 OCA], [https://pdbe.org/7l18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l18 RCSB], [https://www.ebi.ac.uk/pdbsum/7l18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l18 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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| | </div> | | </div> |
| | <div class="pdbe-citations 7l18" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7l18" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[NADPH-Cytochrome P450 Reductase|NADPH-Cytochrome P450 Reductase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: NADPH--hemoprotein reductase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Hubbard, P A]] | + | [[Category: Hubbard PA]] |
| - | [[Category: Kim, J J.K]] | + | [[Category: Kim JJK]] |
| - | [[Category: Shen, A L]] | + | [[Category: Shen AL]] |
| - | [[Category: Xia, C]] | + | [[Category: Xia C]] |
| - | [[Category: Catalytic mechanism]]
| + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Hydride transfer]]
| + | |
| - | [[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 influence of the side chains and positioning of the carboxy-terminal residues of NADPH-cytochrome P450 oxidoreductase (CYPOR) on catalytic activity, structure of the carboxy terminus, and interaction with cofactors has been investigated. A tandem deletion of residues Asp675 and Val676, that was expected to shift the position of the functionally important Trp677, resulted in higher cytochrome c reductase activity than that expected from previous studies on the importance of Asp675 and Trp677 in catalysis. Crystallographic determination of the structure of this variant revealed two conformations of the carboxy terminus. In one conformation (Mol A), the last alpha-helix is partially unwound, resulting in repositioning of all subsequent residues in beta-strand 21, from Arg671 to Leu674 (corresponding to Ser673 and Val676 in the wild type structure). This results in the two C-terminal residues, Trp677 and Ser678, being maintained in their wild type positions, with the indole ring of Trp677 stacked against the isoalloxazine ring of FAD as seen in the wild type structure, and Ser673 occupying a similar position to the catalytic residue, Asp675. The other, more disordered conformation is a mixture of the Mol A conformation and one in which the last alpha-helix is not unwound and the nicotinamide ring is in one of two conformations, out towards the protein surface as observed in the wild type structure (1AMO), or stacked against the flavin ring, similar to that seen in the W677X structure that lacks Trp677 and Ser678 (1JA0). Further kinetic analysis on additional variants showed deletion or substitution of alanine or glycine for Trp677 in conjunction with deletion of Ser678 produced alterations in interactions of CYPOR with NADP(+), 2'5'-ADP, and 2'-AMP, as well as the pH dependence of cytochrome c reductase activity. We postulate that deletion of bulky residues at the carboxy terminus permits increased mobility leading to decreased affinity for the 2'5'-ADP and 2'-AMP moieties of NADP(+) and subsequent domain movement.
Structural and kinetic investigations of the carboxy terminus of NADPH-cytochrome P450 oxidoreductase.,Hubbard PA, Xia C, Shen AL, Kim JP Arch Biochem Biophys. 2021 Apr 15;701:108792. doi: 10.1016/j.abb.2021.108792., Epub 2021 Feb 5. PMID:33556357[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hubbard PA, Xia C, Shen AL, Kim JP. Structural and kinetic investigations of the carboxy terminus of NADPH-cytochrome P450 oxidoreductase. Arch Biochem Biophys. 2021 Apr 15;701:108792. doi: 10.1016/j.abb.2021.108792., Epub 2021 Feb 5. PMID:33556357 doi:http://dx.doi.org/10.1016/j.abb.2021.108792
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