Sandbox 177: Difference between revisions

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CYPOR is a complex, multidomain protein composed of three chains (<scene name='Sandbox_177/Cyporchaina/2'>A</scene>, <scene name='Sandbox_177/Cyporchainb/1'>B</scene>, <scene name='Sandbox_177/Cyporchainc/1'>C</scene>). It also has three different types of associated ligands; one <scene name='Sandbox_177/Cyporfmn/2'>FMN</scene>, three <scene name='Sandbox_177/Cyporfad/2'>FAD</scene> and two <scene name='Sandbox_177/Cypornadph/2'>NADPH</scene> (Fig 1).<ref name="5TSON"/> The three associated binding domains for these ligand types, a connecting domain and a transmembrane anchor make up the important structural elements of CYPOR (Fig 2).   
CYPOR is a complex, multidomain protein composed of three chains (<scene name='Sandbox_177/Cyporchaina/2'>A</scene>, <scene name='Sandbox_177/Cyporchainb/1'>B</scene>, <scene name='Sandbox_177/Cyporchainc/1'>C</scene>). It also has three different types of associated ligands; one <scene name='Sandbox_177/Cyporfmn/2'>FMN</scene>, three <scene name='Sandbox_177/Cyporfad/2'>FAD</scene> and two <scene name='Sandbox_177/Cypornadph/2'>NADPH</scene> (Fig 1).<ref name="5TSON"/> The three associated binding domains for these ligand types, a connecting domain and a transmembrane anchor make up the important structural elements of CYPOR (Fig 2).   


The N-terminus of CYPOR consists of a single alpha-helix that functions as a transmembrane anchor (~6kDa), holding the protein in the endoplasmic reticulum.<ref name="5TSON"/>  The remaining, soluble ~66kDa portion of the protein is responsible for reducing cytochrome P450, consisting of three binding domains for the ligands responsible for the electron flow.<ref name="5TSON"/>  The FMN binding domain is composed of the first 170 residues of the soluble region, which are very similar to those of flavodoxin, another FMN binding protein.<ref name="5TSON"/>  The FAD and NADPH binding domains are located closer to the C-terminus, and are very similar to the FAD domain in ferredoxin-NADP<sup>+</sup> oxidoreductase, both in terms of sequence and structure.<ref name="5TSON"/>
The N-terminus of CYPOR consists of a single alpha-helix that functions as a transmembrane anchor (~6kDa), holding the protein in the endoplasmic reticulum.<ref name="5TSON"/>  The remaining, soluble ~66kDa portion of the protein, responsible for reducing cytochrome P450, consists of three binding domains for the ligands involved in the electron transport chain.<ref name="5TSON"/>  The FMN binding domain is composed of the first 170 residues of the soluble region, which are very similar to those of flavodoxin, another FMN binding protein.<ref name="5TSON"/>  The FAD and NADPH binding domains are located closer to the C-terminus, and are very similar to the FAD domain in ferredoxin-NADP<sup>+</sup> oxidoreductase, both in terms of sequence and structure.<ref name="5TSON"/>


Between the FMN and FAD/NADPH bind domains is a connecting domain, which is a highly flexible random coil.<ref name="5TSON"/>  The hinge region is composed of 12 residues from Gly232 to Arg243, and is highly conserved among most known CYPOR proteins, including those found in humans, rats and even yeast.<ref name="5TSON"/>  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.<ref name="5TSON"/>  Studies that examined the rate of electron transfer within CYPOR seem to confirm this, as electron transfer rate appears to decrease proportionally to increases in the viscosity of the fluid medium it is in.<ref name="5TSON"/> When residues within the the hinge are mutated so it is no longer flexible, studies have found that CYPOR cannot effectively transfer electrons to cytochrome P450, unless there is a high electron pool available.<ref name="5TSON"/>  This indicates that without the hinge movement electrons are not able to be efficiently moved from FAD to FMN, decreasing the reductase capabilities of CYPOR.<ref name="5TSON"/>  These surface proteins are  
Between the FMN and FAD/NADPH bind domains is a connecting domain, which is a highly flexible random coil.<ref name="5TSON"/>  The hinge region is composed of 12 residues from Gly232 to Arg243, and is highly conserved among most known CYPOR proteins, including those found in humans, rats and even yeast.<ref name="5TSON"/>  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.<ref name="5TSON"/>  Studies that examined the rate of electron transfer within CYPOR seem to confirm this, as electron transfer rate appears to decrease proportionally to increases in the viscosity of the fluid medium it is in.<ref name="5TSON"/> When residues within the the hinge are mutated so it is no longer flexible, studies have found that CYPOR cannot effectively transfer electrons to cytochrome P450, unless there is a high electron pool available.<ref name="5TSON"/>  This indicates that without the hinge movement electrons are not able to be efficiently moved from FAD to FMN, decreasing the reductase capabilities of CYPOR.<ref name="5TSON"/>  These surface proteins are


==='''Function'''===
==='''Function'''===
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