Sandbox Reserved 434: Difference between revisions

4CYG is a key protein that is involved in the breakdown of pantetheine to panthothenic acid and cysteamine. These proteins are associated with many metabolic diseases like type 2 diabetes. Understanding the binding interaction would give insight into treating these diseases more effectively. 4CYG has three <scene name='48/483891/Binding_site/1'>Catalytic Residues</scene> (Glu79, Lys178 and Cys211) that represents the active site of the enzyme. The purple amino acids represent the three amino acids directly involved in the binding interactions. The active site is located in the center of the enzyme in between the two sub-units. It was discovered that Glu79 and Lys178 were responsible for orienting and activating Cys211 to catalyze the reaction. The substrate forms a covalent bond with Cys211 producing the transition state.[1]

In addition, the two residues <scene name='48/483891/Glu249_and_glu439/2'>GLU249 AND GLU439</scene> are essential for enzymatic function too. The purple regions are polar whereas the grey regions are hydrophobic. The two black amino acids represent GLU249 and GLU439. The two glutamic acid residues are both located in hydrophobic regions 4 Angstroms away. Although this is energetically unfavorable to have a polar amino acid in a nonpolar region, these two amino acids help maintain the structure between the two sub-units for proper binding interactions to occur.[1]

The importance of pantetheinase stems from the vitality of the components of the reaction it catalyzes. It is for this reason that pantetheinase has been a promising point of research in the field of medicine. Pantetheine analogues known as pantothenamides have been shown to act as effective antibiotics that protect the body from bacterial intruders. The similarity of these analogues to pantetheine allows for the active sites on pantetheinase to catalyze their breakdown through hydrolysis. The administration of RR6 in the presence of pantetheinase and other antibiotic pantothenamides revealed that RR6 acts as a competitive inhibitor with great affinity for the active sites on pantetheinase, thus preserving desired concentrations of the pantothenamides with antibiotic characteristics. The RR6 inhibitor is shown below.