4y7c: Difference between revisions
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The | ==rat CYPOR mutant - G141del/E142N== | ||
<StructureSection load='4y7c' size='340' side='right'caption='[[4y7c]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4y7c]] 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=4Y7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y7C FirstGlance]. <br> | |||
</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='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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4y7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y7c OCA], [https://pdbe.org/4y7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y7c RCSB], [https://www.ebi.ac.uk/pdbsum/4y7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y7c ProSAT]</span></td></tr> | |||
</table> | |||
== 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
NADPH-Cytochrome P450 oxidoreductase (CYPOR) transfers electrons from NADPH to cytochromes P450 via its FAD and FMN. To understand the biochemical and structural basis of electron transfer from FMN-hydroquinone to its partners, three deletion-mutants in a conserved loop near the FMN were characterized. Comparison of oxidized and reduced wild type and mutant structures reveals that the basis for the air-stability of the neutral-blue semiquinone is protonation of the flavin N5 and strong H-bond formation with the Gly-141 carbonyl. The Gly-143 protein had moderately decreased activity with cytochrome P450 and cytochrome c. It formed a flexible loop, which transiently interacts with the flavin N5, resulting in the generation of both an unstable neutral-blue semiquinone and hydroquinone. The Gly-141 and Gly-141/Glu-142Asn mutants were inactive with cytochrome P450, but fully active with reduced cytochrome c . In the Gly-141 mutants, the backbone amide of Glu/Asn 142 forms an H-bond to the N5 of the oxidized flavin, which leads to formation of an unstable red-anionic semiquinone with a more negative potential than the hydroquinone. The semiquinone of G141/E142N was slightly more stable than that of G141, consistent with its crystallographically demonstrated more rigid loop. Nonetheless, both Gly-141 red semiquinones were less stable than those of the corresponding loop in cytochrome P450 BM3 and the nNOS mutant (DeltaGly-810). Our results indicate that the catalytic activity of CYPOR is a function of the length, sequence, and flexibility of the 140s loop and illustrate the sophisticated variety of biochemical mechanisms employed in fine-tuning its redox properties and function. | |||
Mutants of Cytochrome P450 Reductase Lacking Either Gly-141 or Gly-143 Destabilize Its FMN Semiquinone.,Rwere F, Xia C, Im S, Haque MM, Stuehr DJ, Waskell L, Kim JP J Biol Chem. 2016 May 9. pii: jbc.M116.724625. PMID:27189945<ref>PMID:27189945</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4y7c" style="background-color:#fffaf0;"></div> | ||
[[Category: Kim | |||
==See Also== | |||
*[[NADPH-Cytochrome P450 Reductase|NADPH-Cytochrome P450 Reductase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Kim JJP]] | |||
[[Category: Xia C]] | |||