Sandbox 177: Difference between revisions

Specifically a hydride anion is moved from NADPH to the FAD.<ref name="5TSON"/>  The two electrons are then individually passed to FMN, in a process that is believed to be conformationally gated.<ref name="5TSON"/>  As previously discussed in the structure section, this belief is based upon the fact that electrons do not appear to be able to be transferred from FAD to FMN unless the two ligands are in close proximity.<ref name="5TSON"/>  The protein accomplishes this by undergoing a conformational change, believed to occur because of the flexibility of the hinge domain, which brings the flavin isoalloxazine rings of FMN and FAD into close proximity to one another.<ref name="5TSON"/>  In this closed conformation van der Waals forces help hold the ligands together, allowing for efficient electron movement.<ref name="5TSON"/>  However, for CYPOR to transfer the electrons, again one at a time, from FMN to cytochrome P450, CYPOR cannot be in a closed conformation because it prevents cytochrome P450 from being able to access FMN.<ref name="5TSON"/>  As a result CYPOR must undergo another conformational change so it is in an open conformation allowing the necessary surface residues on the FMN binding domain to form interactions with cytochrome P450 for electron transfer to occur (Fig 2).<ref name="5TSON"/> These surface residues have been found to have an increased number of carboxyl containing amino acids (Aspartate and glutamate), which gives this area a negative charge (Fig 2).<ref name="7aTSON">PMID:1929397</ref><ref name="7bTSON">PMID:3016501</ref> The carboxyl groups can then bind basic residues like leucine found on cytochrome P450 to correctly orient the two proteins for electron transfer.<ref name="7aTSON"/><ref name="7bTSON"/>  Additionally, cytochrome P450 can have an induced dipole moment across it, with a partial positive charge occurring on the side of the protein where the internal heme is closest to the surface of the protein (Fig 2). <ref name="7aTSON"/><ref name="7bTSON"/>  The partial positive charge interacting with the previously mentionned acidic residues of CYPOR is thought to help solidify the interaction between CYPOR and cytochrome P450 in the best orientation for electron transfer.<ref name="7aTSON"/><ref name="7bTSON"/>