Sandbox Reserved 1475: Difference between revisions

The crystal structure was cocrystallized with <scene name='80/800654/Nad/1'>NAD</scene>, and was determined at a 2.7 Angstrom resolution ([[Figure 2]] Chain D present with NAD represented in pink).<ref name="Lamb AL, Newcomber ME" /> NAD+ acts as a cofactor and is the electron acceptor in RalDH2 oxidoructase reaction as seen in the reaction presented above. RalDH2 has to be folded in a proper manner for its enzymatic function to occur. The folding of the enzyme is partially due to the interactions of NAD+ and Chloride ions. When NAD+ is present hydrogen bonds with Glu and Ser form, van der Waals interactions with non-polar residues and one polar residue (Lys) forms. The interaction with Lys-192 provides the transition state stability, making for a favorable confirmation.<ref name="Lamb AL, Newcomber ME" /> This conformational change is important since in the absence of NAD+, no crystal structures grew in any of the screened conditions.<ref name="Lamb AL, Newcomber ME" />  The Chloride ions participate in hydrophobic interactions with Arg which also help maintain the folded structure.<ref name="Lamb AL, Newcomber ME" /> 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.