Group:SMART:2010 Pingry SMART Team: Difference between revisions

Rat liver 3-alpha-hydroxysteroid dihydrodiol dehydrogenase is often abbreviated to 3α-HSD.  

 

<scene name='2010_Pingry_SMART_Team/1lwi_default/5'>Non-polar cavity for substrate binding is colored CPK. Leu54, Tyr55, Trp86, Phe118, Phe129, and Tyr216 are hydrophobic amino acids found in the pocket.</scene> The reason why the substrate binding pocket is non-polar is that the substrate, testosterone, is a lipid and therefore hydrophobic. This is an important factor when considering how to modify substrate specificity. In Dr. Banta's fuel cell protein, the most common substrate will probably be some type of sugar, which is a hydrophilic molecule. Therefore, the substrate binding pocket must match the substrate. The catalytic triad, which includes the most important amino acids in regards to reacting with the substrate is at the distal, or far, end of the pocket.

<scene name='2010_Pingry_SMART_Team/1lwi_catalytic_triad/1'>Cyan highlights the catalytic triad: Tyr55, Asp50, and Lys84.</scene> These three amino acids perform a reaction called a proton relay to transfer electrons between substrate and cofactor. 3α-HSD is capable of running the reaction both ways, either oxidizing or reducing the substrate and cofactor depending on the state in which testosterone must be. Tyr55 acts as acid, donates proton to steroid-->Tyr55 forms hydrogen bond to Lys84 to stabilize-->Lys84 forms salt link to Asp50 for further stability. In Dr. Banta's protein, this reaction must only be run so that the sugar will be oxidized to reduce the cofactor. The transfer of electrons from cofactor to circuit is already fairly efficient, but the key to an efficient reaction is in transfering the electron from substrate to cofactor. This is where the catalytic triad is extremely important.