User:Christopher French: Difference between revisions

The catalytic triad in caspase 8 comprises Cys360, His317, and Arg258. The carboxyl group of P1 aspartate forms a salt bridge with Arg413 and Arg260. It also forms hydrogen bonds to Gln358. The P1 α-carbonyl group rotates and the oxygen atom rehybridizes to become a hydroxyl group. This then forms a hydrogen bond with the imidazole group of His317. A clear interaction exists between the carbonyl oxygen of Arg258 and the Nє of His317. The S2 pocket Cγ atom of the threonine sidechain of P2 lies in a hydrophobic pocket that is formed from the sidechains of Val410 and Tyr412. The Oγ is surrounded by water molecules. The S3 pocket consists of a glutamate at P3 that sits in a cleft made by Arg413, Arg258, and Pro415, and Asn261. Arg413 forms a salt bridge to P3 glutamate and P1 aspartate sidechains. Arg413 also forms hydrogen bonds between its main chain atoms and the mainchain if the peptide inhibitor. The S4 pocket is especially important in selectivity. The acetyl of the inhibitor hydrogen bonds to the carboxyl group of P3 glutamate through a hydrogen bond. The hydrogen bond participants then move away to accommodate a non-polar residue. The faces of two aromatic residues, Trp420 and Tyr412 help form part of the hydrophobic S4 pocket.