Sandbox Reserved 1475: Difference between revisions
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With the cofactor NAD+ present the catalytic domain of RalDH2 is highly mobile and needs the selective substrate present to immobilize the catalytic domain. The binding of hydrophobic substrate and the NAD+ cofactor are needed to stabilize the catalytic domain.<ref name="Lamb AL, Newcomber ME" /> Short chain aldehydes do not have a large enough hydrophobic surface to bury inside the channel and therefor cannot work as suitable substrates. The long tails of the long chained aldehydes are needed to interact with the catalytic Cys-302 through hydrogen bonds. Short chained aldehydes can have hydrogen bond interactions with Cys-302 however are not large enough to fully bury the whole access channel, which is needed for the catalytic domain to be immobilized. | With the cofactor NAD+ present the catalytic domain of RalDH2 is highly mobile and needs the selective substrate present to immobilize the catalytic domain. The binding of hydrophobic substrate and the NAD+ cofactor are needed to stabilize the catalytic domain.<ref name="Lamb AL, Newcomber ME" /> Short chain aldehydes do not have a large enough hydrophobic surface to bury inside the channel and therefor cannot work as suitable substrates. The long tails of the long chained aldehydes are needed to interact with the catalytic Cys-302 through hydrogen bonds. Short chained aldehydes can have hydrogen bond interactions with Cys-302 however are not large enough to fully bury the whole access channel, which is needed for the catalytic domain to be immobilized. | ||
As seen in [[Figure 5]] <ref name="Km value chart">Wang, Xianshu. Penzes, Peter., Napoli, Joseph L., Cloning of a cDNA Encoding an Aldehyde Dehydrogenase and Its Expression in ''Escherichia coli'' RECOGNITION OF RETINAL AS SUBSTRATE. J. Biol. Chem. (1996) 271:16288-16293. doi:10.1074/jbc.271.27.16288 </ref> | |||
In [[Figure 5]] it is visible to see that acetaldehyde and benzaldehyde both have really high Km values, 645uM and 305uM respectfully, and relatively low Vmax values, 139nmol/min/mg and 200nmol/min/mg respectfully. Octantal and decanal both have really low Km values, 5uM and 3uM respectfully, and relatively high Vmax values, 152nmol/min/mg and 214nmol/min/mg respectfully. Acetaldehyde and benzaldehyde are both short chained aldehydes compared to octantal and decanal aldehydes. It is easier to compare the ratio of Vmax/Km. An energetically favorable substrate would display a ratio of Vmax/Km that has a large magnitude. As seen in [[Figure 5]], both the long chained octantal and decanal aldehydes had large Vmax/Km values, 152 AND 214 respectfully. The substrate that RalDH2 uses to actually convert Vitamin A (Retinol) to retinoic acid is retinal in its "all-trans" form. As seen in [[Figure 5]] the Km value for the this substrate is the smallest out all that were tested, and the Vmax values was comparatively high. The Vmax/Km was also pretty large at a value of 49± 6. | |||
<ref name="Km value chart">Wang, Xianshu. Penzes, Peter., Napoli, Joseph L., Cloning of a cDNA Encoding an Aldehyde Dehydrogenase and Its Expression in ''Escherichia coli'' RECOGNITION OF RETINAL AS SUBSTRATE. J. Biol. Chem. (1996) 271:16288-16293. doi:10.1074/jbc.271.27.16288 </ref> | |||
== Disease == | == Disease == | ||
