Chymotrypsin 7060 218963091 2008-06-12T23:28:26Z 82.4.87.24 {{protein | Name = chymotrypsinogen B1 | caption = | image = 1AB9.png | width = 150 px | HGNCid = 2521 | Symbol = CTRB1 | AltSymbols = CTRB | EntrezGene = 1504 | OMIM = 118890 | RefSeq = NM_001906 | UniProt = P17538 | PDB = | MEROPS = S01.152 | ECnumber = 3.4.21.1 | Chromosome = 16 | Arm = q | Band = 23.1 | LocusSupplementaryData = }} {{protein | Name = chymotrypsinogen B2 | caption = | image = | width = | HGNCid = 2522 | Symbol = CTRB2 | AltSymbols = | EntrezGene = 440387 | OMIM = | RefSeq = NM_001025200 | UniProt = Q6GPI1 | PDB = | ECnumber = | Chromosome = 16 | Arm = q | Band = 22.3 | LocusSupplementaryData = }} {{protein | Name = chymotrypsin C (caldecrin) | caption = | image = | width = | HGNCid = 2523 | Symbol = CTRC | AltSymbols = | EntrezGene = 11330 | OMIM = 601405 | RefSeq = NM_007272 | UniProt = Q99895 | MEROPS = S01.157 | PDB = | ECnumber = | Chromosome = 1 | Arm = p | Band = 36.21 | LocusSupplementaryData = }} '''Chymotrypsin''' (bovine γ chymotrypsin: {{PDB|1AB9}}, {{EC number|3.4.21.1}}) is a digestive enzyme that can perform [[proteolysis]]. Chymotrypsin cleaves peptides at the carboxyl side of [[tyrosine]], [[tryptophan]], and [[phenylalanine]] because these three [[amino acid]]s contain [[aromatic]] rings. Over time, chymotrypsin also hydrolyzes other amide bonds, particularly those with [[leucine]]-donated carboxyls. ==Activation of chymotrypsin== Chymotrypsin is synthesized in the [[pancreas]] by [[protein biosynthesis]] as a [[wiktionary:Precursor|precursor]] called [[chymotrypsinogen]] that is enzymatically inactive. On cleavage by [[trypsin]] into two parts that are still connected via an S-S bond, cleaved chymotrypsinogen molecules can activate each other by removing two small peptides in a ''trans''-proteolysis. The resulting molecule is active chymotrypsin, a three [[peptide|polypeptide]] molecule interconnected via [[disulfide bond]]s. ==Action and kinetics of chymotrypsin== ''In vivo'', chymotrypsin is a proteolytic enzyme acting in the digestive systems of mammals and other organisms. It facilitates the cleavage of peptide bonds by a [[hydrolysis]] reaction, a process which albeit thermodynamically favourable, occurs extremely slowly in the absence of a catalyst. The main substrates of chymotrypsin include [[tryptophan]], [[tyrosine]], [[phenylalanine]], [[leucine]], and [[methionine]], which are cleaved at the carboxyl terminal. Like many proteases, chymotrypsin will also hydrolyse ester bonds ''in vitro'', a virtue that enabled the use of substrate analogs such as N-acetyl-L-phenylalanine p-nitrophenyl ester for enzyme assays. [[Image:Mechanismus.gif|thumb|left|450px|Mechanism of peptide bond cleavage in α-chymotrypsin]] Chymotrypsin cleaves peptide bonds by attacking the unreactive carbonyl group with a powerful nucleophile, the serine 195 residue located in the active site of the enzyme, which briefly becomes covalently bonded to the substrate, forming an enzyme-substrate intermediate. These findings rely on inhibition assays and the study of the kinetics of cleavage of the aforementioned substrate, exploiting the fact that the enzyme-substrate intermediate [[4-Nitrophenol|''p''-nitrophenolate]] has a yellow colour, enabling us to measure its concentration by measuring light absorbance at 405 nm. It was found that the reaction of chymotrypsin with its substrate takes place in two stages, an initial “burst” phase at the beginning of the reaction and a steady-state phase following [[Michaelis-Menten kinetics]].It is also called "ping-pong" mechanism. The mode of action of chymotrypsin explains this as hydrolysis takes place in two steps. First acylation of the substrate to form an acyl-enzyme intermediate and then deacylation in order to return the enzyme to its original state. ==References== *Stryer et al. (2002). ''Biochemistry'' (5th ed.). New York: Freeman. ISBN 0716746840. *Garrett & Grisham. (2004). ''Biochemistry'' (3rd ed.). Brooks Cole. ISBN 0534490336. ==External links== * {{MeshName|Chymotrypsin}} {{Serine endopeptidases}} [[Category:EC 3.4.21]] [[Category:Enzymes]] [[de:Chymotrypsin]] [[es:Quimotripsina]] [[fr:Chymotrypsine]] [[he:כימוטריפסין]] [[ja:キモトリプシン]] [[no:Chymotrypsin]] [[pl:Chymotrypsyna]] [[pt:Quimotripsina]] [[fi:Kymotrypsiini]] [[sv:Kymotrypsin]] [[zh:胰凝乳蛋白酶]]