Ann Taylor sandbox 11

From Proteopedia

The Mechanism of Trypsin

spinqualitylabelsall models PDB ID 2agg Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2agg, resolution 1.28Å ()
Ligands:	,
Non-Standard Residues:
Activity:	Trypsin, with EC number 3.4.21.4
Related:	2age, 2agi, 2ah4
Structural annotation: Resources: CATH : 2Aggx02, 2Aggx01 InterPro : Ipr001254, Ipr018114, Ipr009003, Ipr001314 Pfam : PF00089 SCOP : d2aggx1
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Trypsin is a serine protease that is used in the digestive system. It cleaves on the C terminal side of arginine or lysine residues. This specificity is due to the presence of an at the bottom of the binding pocket.

Trypsin cleaves peptides via a covalent catalysis mechanism--that is, it forms a covalent intermediate between the substrate and itself, which is then cleaved by reaction with water. This structure shows the covalent interaction between , succinyl-ala-ala-pro-lys (pdb code 2agg). The catalytic triad of Serine 195, Histidine 57 and Aspartic acid 102 are the key residues involved in the mechanism. After binding to the substrate, serine 195 nucleophilically attacks the carbonyl group of the cationic amino acid of the substrate. His57 and asp102 assist in the catalysis by increasing the nucleophilicity of the serine residue and by donating a proton to the leaving peptide group. This dual role of deprotonating serine and protonating the leaving peptide is facilitated by a shift in the position of the His 57 residue.^[1]

1. ↑ Radisky ES, Lee JM, Lu CJ, Koshland DE Jr. Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates. Proc Natl Acad Sci U S A. 2006 May 2;103(18):6835-40. Epub 2006 Apr 24. PMID:16636277