Isocitrate dehydrogenase

Overview:Overview:

Isocitrate Dehydrogenase is an enzyme that is used during the third step of the citric acid cycle. This biological reaction is an essential process that is used to create molecules that are used for cellular energy. In this step it catalyzes the oxidative decarboxylation of isocitrate meaning that CO2 is released from the isocitrate. In addition coenzyme NAD+ is converted to an NADH. This reaction results in an alpha-ketoglutarate molecule which is then moved on to the forth step of the citric acid cycle.

Structure:Structure:

Isocitrate dehydrogenase is SCOP classified as an alpha beta structure. Its secondary composition consists of mainly alpha helices and beta sheets which are arranged into three layer alpha beta alpha sandwich structures. The entire protein consists of two side by side sandwich structures that face opposite directions. This then causes the proteins two active sites to face opposite directions. These two groups make up the A and B subunits of isocitrate dehydrogenase.

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The Active SiteThe Active Site

The active site of Isocitrate dehydrogenase binds the NAD+ or an NADP+ molecule as well as an Mn+ or Ca2+. This metal ion seems to be essential for catalysis. Side chains of Asp 279 form hydrogen bonds with Ser94 (Human isocitrate dehydrogenase). Isocitrate is able to bind to the active site using about 8 amino acids like tyrosine, serine, asparagine, arginine, arginine, arginine, tyrosine, and lysine. Across species these are not perfectly conserved by they are replaced with residues of similar properties and also are found in similar areas of the protein. Below is a picture of Porcine Active site with all of its residuals and ligands.

The blue is the Mn+ ion next to the ligand which is surrounded by the residuals of that active site.