Active centre in chymotrypsin

Chymotrypsin, in addition to its proteolytic activity, can also function as an esterase. It is inactivated by D.F.P., etc. (p. 186). The esterases firmly bind the phosphorus of D.F.P., and in the case of chymotrypsin the reaction is bimolecular, yielding a crystalline derivative containing two isopropoxy groups and one atom of phosphorus per protein molecule, but no fiuorine. Recently the compound of chymotrypsin and labelled D.F.P. has been hydrolysed and the hydrolysate shown to contain L-serine phosphoric acid. The latter is known to be phosphoryl-ated on its hydroxyl group.  

Recently the compound of chymotr3rpsin and labelled D.F.P. has been hydrolysed and the hydrolysate shown to contain L-serine phosphoric acid. The latter is known to be phosphoryl-ated on its hydroxyl group.  

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Direct evidence for the 7)resence of histidiii in the active centre of Chymotrypsin. Biochemistry 2, 252 255 (1963). 

McLachlan and Shotton have proposed a threo-dimensional model for a-lytic protease based on the. y-ray structures of a-chymotrypsin and elastase. They suggest that the differences are chiefly on the surface where entire loops are missing and a new one is added as shown in Figure 1. The hydrophobic core thus remains virtually unaltered, so that the two halves of the molecule form an active centre similar to that of elastase. 

Figure 1 Ribbon diagram of the polypeptide conformation of a-lytic protease drawn on the known skeleton of a-chymotrypsin. Shaded areas are present in chymotrypsin but probably missing in the a-lytic protease dotted lines are short cuts striped sections are insertions beaded lines are disulphide bridges dark bars are cuts to allow insertions. The active site is in the centre...

Besides chlorinated pesticides, some of the phosphorous pesticides are also chiral (see Table 2.1). The phosphorous pesticides also differ in their enantioselective toxicities. These pesticides were introduced in the 1950s to control insects in fruit, vegetables and other crops. Malathion is biotransformed into a racemic malaxon that has anti-acetylcholinesterate (insecticidal) activity. The /f-enantiomer has a 22 times greater inhibitory potency than the 5-enantiomer for bovine erythrocyte cholinesterase [39, 40]. The nerve agent, soman, has two chiral centres, and the two (—)-diastereoisomers are more potent inhibitors than their corresponding (-1-)-counteiparts for acetylcholinesterase and a-chymotrypsin. 

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