Chymotrypsin

Chymotrypsin
chymotrypsin
ChymotrypsinA1.jpg
Crystallographic structure of Bos taurus chymotrypsinogen.[1]
Identifiers
EC number 3.4.21.1
CAS number 9004-07-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
chymotrypsin C
Identifiers
EC number 3.4.21.2
CAS number 9036-09-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

Chymotrypsin is a digestive enzyme that can perform proteolysis.[2] Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond (the P1 position) is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a 'hydrophobic pocket' (the S1 position) of the enzyme. The hydrophobic and shape complementarity between the peptide substrate P1 sidechain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme.[3][4] Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine at the P1 position.

Contents

Activating chymotrypsinogen into chymotrypsin

Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a 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-polypeptide molecule interconnected via disulfide bonds.

Action and kinetics of chymotrypsin

In vivo, chymotrypsin is a proteolytic enzyme (Serine protease) acting in the digestive systems of mammals and other organisms. It facilitates the cleavage of peptide bonds by a hydrolysis reaction, which despite being 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 amide bonds in vitro, a virtue that enabled the use of substrate analogs such as N-acetyl-L-phenylalanine p-nitrophenyl amide for enzyme assays.

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 p-nitrophenolate has a yellow colour, enabling us to measure its concentration by measuring light absorbance at 410 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.

Isozymes

chymotrypsinogen B1
Identifiers
Symbol CTRB1
Entrez 1504
HUGO 2521
OMIM 118890
RefSeq NM_001906
UniProt P17538
Other data
EC number 3.3.21.1
Locus Chr. 16 q23.1
chymotrypsinogen B2
Identifiers
Symbol CTRB2
Entrez 440387
HUGO 2522
RefSeq NM_001025200
UniProt Q6GPI1
Other data
EC number 3.3.21.1
Locus Chr. 16 q22.3
chymotrypsin C (caldecrin)
Identifiers
Symbol CTRC
Entrez 11330
HUGO 2523
OMIM 601405
RefSeq NM_007272
UniProt Q99895
Other data
EC number 3.3.21.2
Locus Chr. 1 p36.21

References

  1. ^ PDB 1CHG; Freer ST, Kraut J, Robertus JD, Wright HT, Xuong NH (April 1970). "Chymotrypsinogen: 2.5-angstrom crystal structure, comparison with alpha-chymotrypsin, and implications for zymogen activation". Biochemistry 9 (9): 1997–2009. doi:10.1021/bi00811a022. PMID 5442169. 
  2. ^ Wilcox PE (1970). "Chymotrypsinogens — chymotrypsins". Methods in Enzymology. Methods in Enzymology 19: 64–108. doi:10.1016/0076-6879(70)19007-0. ISBN 978-0-12-181881-4. 
  3. ^ Appel W (December 1986). "Chymotrypsin: molecular and catalytic properties". Clin. Biochem. 19 (6): 317–22. doi:10.1016/S0009-9120(86)80002-9. PMID 3555886. 
  4. ^ Berger A, Schechter I (February 1970). "Mapping the active site of papain with the aid of peptide substrates and inhibitors". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 257 (813): 249–64. doi:10.1098/rstb.1970.0024. PMID 4399049. 

Further reading

  • Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0. 
  • Grisham CM, Reginald H (2005). Biochemistry. Australia: Thomson Brooks/Cole. ISBN 0-534-49033-6. 

External links


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Look at other dictionaries:

  • Chymotrypsin B — Bändermodell von Chymotrypsin nach PDB  …   Deutsch Wikipedia

  • Chymotrypsin-C — (caldecrin) Identifiers Symbols CTRC; CLCR; ELA4 External IDs OMIM …   Wikipedia

  • Chymotrypsin — B Größe 241 = 13+131+97 AA Precursor Chymotrypsinogen B (245 AA) Bezeich …   Deutsch Wikipedia

  • Chymotrypsin — Chymotrypsin, zu den Endopeptidasen (⇒ Proteasen) gehörendes, Proteine zu Oligopeptiden spaltendes Verdauungsenzym der Wirbeltiere, das sein pH Optimum im alkalischen Bereich (pH 7–8) hat und bevorzugt Peptidbindungen spaltet, deren… …   Deutsch wörterbuch der biologie

  • chymotrypsin — [kī΄mō trip′sin] n. [< Gr chymos (see CHYME) + TRYPSIN] a pancreatic enzyme that is important in the digestion of proteins in the intestines …   English World dictionary

  • Chymotrypsin — Chy|mo|tryp|sin [↑ Chymo u. ↑ Trypsin], das; s, e: in der Bauchspeicheldrüse aus Vorstufen (Chymotrypsinogenen) gebildete Verdauungsenzyme (↑ Proteinasen), die auch med. Verwendung in der Wundheilung u. Ödemtherapie finden. * * * Chymotrypsin  … …   Universal-Lexikon

  • chymotrypsin — C. A or B; a serine proteinase of the gastrointestinal tract that preferentially cleaves carboxyl links of hydrophobic amino acid s, particularly at tyrosyl, tryptophanyl, phenylalanyl, and leucyl residues; synthesized in the pancreas as… …   Medical dictionary

  • chymotrypsin — n. a protein digesting enzyme (see peptidase). It is secreted by the pancreas in an inactive form, chymotrypsinogen, that is converted into chymotrypsin in the duodenum by the action of trypsin …   The new mediacal dictionary

  • chymotrypsin — chimotripsinas statusas T sritis chemija apibrėžtis Proteazė, skaidanti Phe, Tyr, Trp karboksigrupių sudarytus peptidinius ryšius. atitikmenys: angl. chymotrypsin rus. химотрипсин …   Chemijos terminų aiškinamasis žodynas

  • chymotrypsin — noun Etymology: chyme + o + trypsin Date: 1933 a protease that hydrolyzes peptide bonds and is formed in the intestine from chymotrypsinogen • chymotryptic adjective …   New Collegiate Dictionary

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