Sandbox 177: Difference between revisions
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<applet load='3es9' size='250' color='black' frame='true' align='right' scene='Sandbox_177/Jmol3es9/1' caption='NADPH-cytochrome P450 oxidoreductase - Secondary structures are blue, random coils are white and ligands are yellow' /> | <applet load='3es9' size='250' color='black' frame='true' align='right' scene='Sandbox_177/Jmol3es9/1' caption='NADPH-cytochrome P450 oxidoreductase - Secondary structures are blue, random coils are white and ligands are yellow' /> | ||
Taya O'Neill | Taya O'Neill | ||
==General Information== | ==='''General Information'''=== | ||
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NADPH-cytochrome P450 oxidoreductase (CYPOR) is a ~78kDa, multidomain flavoprotein. <ref name="5TSON">PMID:19171935</ref> Containing three co-factors, FMN, FAD and NADPH, CYPOR is the archetype for the mammalian diflavin-containing enzyme family.<ref name="5TSON"/> | NADPH-cytochrome P450 oxidoreductase (CYPOR) is a ~78kDa, multidomain flavoprotein. <ref name="5TSON">PMID:19171935</ref> Containing three co-factors, FMN, FAD and NADPH, CYPOR is the archetype for the mammalian diflavin-containing enzyme family.<ref name="5TSON"/> | ||
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Regulation of this protein, which is found all tissues to some extent, is largely at the transcriptional level.<ref name="3cTSON">PMID:11306680</ref> The thyroid hormone T3 in most cases, while adrenocorticotrophic hormone acts as a regulator in a few specific cases.<ref name="3aTSON">PMID:2495435</ref><ref name="3bTSON">PMID:1737785</ref> | Regulation of this protein, which is found all tissues to some extent, is largely at the transcriptional level.<ref name="3cTSON">PMID:11306680</ref> The thyroid hormone T3 in most cases, while adrenocorticotrophic hormone acts as a regulator in a few specific cases.<ref name="3aTSON">PMID:2495435</ref><ref name="3bTSON">PMID:1737785</ref> | ||
==Structure== | ==='''Structure'''=== | ||
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CYPOR is a multidomain protein. The N-terminus consists of a single alpha-helix that functions as a transmembrane anchor (~6kDa), holding the protein in the endoplasmic reticulum. The portion of the protein responsible for reducing cytochrome P450 is soluble and ~66kDa. The first 170 residues of the soluble region are very similar to those of flavodoxin, which correlates to the fact that this is the area that binds FMN. The FAD and NADPH binding domain is located in the C-terminal section. Between the FMN and FAD/NADPH bind domains is a connecting domain, which is a random coil and highly flexible. This section is presumed to be responsible for the relatively increased mobility of the FMN domain, changes to conformation and the relative orientation of the binding domains. Because of this, it plays a key role in the transfer of electrons between FMN and FAD. <ref name="5TSON"/> | CYPOR is a multidomain protein. The N-terminus consists of a single alpha-helix that functions as a transmembrane anchor (~6kDa), holding the protein in the endoplasmic reticulum. The portion of the protein responsible for reducing cytochrome P450 is soluble and ~66kDa. The first 170 residues of the soluble region are very similar to those of flavodoxin, which correlates to the fact that this is the area that binds FMN. The FAD and NADPH binding domain is located in the C-terminal section. Between the FMN and FAD/NADPH bind domains is a connecting domain, which is a random coil and highly flexible. This section is presumed to be responsible for the relatively increased mobility of the FMN domain, changes to conformation and the relative orientation of the binding domains. Because of this, it plays a key role in the transfer of electrons between FMN and FAD. <ref name="5TSON"/> | ||
==Function== | ==='''Function'''=== | ||
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[[Image:CPR chargepair.gif|thumb|right|250px|Electrostatic charge pairing between Cyt P450 and the FMN binding domain induces the interaction between CYPOR and Cyt P450.]] | [[Image:CPR chargepair.gif|thumb|right|250px|Electrostatic charge pairing between Cyt P450 and the FMN binding domain induces the interaction between CYPOR and Cyt P450.]] | ||
''In vivo'' CYPOR is believe to alternate between a one and a three electron reduced form. While the 1 electron form is fairly stable, forming a neutral blue semiquinone, it is the hydroquinone, or 3 electron form, that is able to donate electrons to the desired redox partners. | ''In vivo'' CYPOR is believe to alternate between a one and a three electron reduced form. While the 1 electron form is fairly stable, forming a neutral blue semiquinone, it is the hydroquinone, or 3 electron form, that is able to donate electrons to the desired redox partners. | ||
