1trn is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
TRY1_HUMAN Defects in PRSS1 are a cause of pancreatitis (PCTT) [MIM:167800. A disease characterized by the presence of calculi in pancreatic ducts. It causes severe abdominal pain attacks.[1][2][3][4][5][6][7][8][9][10][11]
Function
TRY1_HUMAN Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.[12]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The X-ray structure of human trypsin 1 has been determined in the presence of diisopropyl-phosphofluoridate by the molecular replacement method and refined at a resolution of 2.2 A to an R-factor of 18%. Crystals belong to the space group P4, with two independent molecules in the asymmetric unit packing as crystallographic tetramers. This study was performed in order to seek possible structural peculiarities of human trypsin 1, suggested by some striking differences in its biochemical behavior as compared to other trypsins of mammalian species. Its fold is, in fact, very similar to those of the bovine, rat and porcine trypsins, with root-mean-square differences in the 0.4 to 0.6 A range for all 223 C alpha positions. The most unexpected feature of the human trypsin 1 structure is in the phosphorylated state of tyrosine residue 151 in the present X-ray study. This feature was confirmed by mass spectrometry on the same inhibited sample and also on the native enzyme. This phosphorylation strengthens the outstanding clustering of highly negative or highly positive electrostatic surface potentials. The peculiar inhibitory behaviour of pancreatic secretory trypsin inhibitors of the Kazal type on this enzyme is discussed as a possible consequence of these properties. A charged surface loop has also been interpreted as an epitope site recognised by a monoclonal antibody specific to human trypsin 1.
Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151.,Gaboriaud C, Serre L, Guy-Crotte O, Forest E, Fontecilla-Camps JC J Mol Biol. 1996 Jun 28;259(5):995-1010. PMID:8683601[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Teich N, Ockenga J, Hoffmeister A, Manns M, Mossner J, Keim V. Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation. Gastroenterology. 2000 Aug;119(2):461-5. PMID:10930381
↑Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet. 1996 Oct;14(2):141-5. PMID:8841182 doi:10.1038/ng1096-141
↑Teich N, Bauer N, Mossner J, Keim V. Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants. Am J Gastroenterol. 2002 Feb;97(2):341-6. PMID:11866271 doi:10.1111/j.1572-0241.2002.05467.x
↑Gorry MC, Gabbaizedeh D, Furey W, Gates LK Jr, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterology. 1997 Oct;113(4):1063-8. PMID:9322498
↑Witt H, Luck W, Becker M. A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis. Gastroenterology. 1999 Jul;117(1):7-10. PMID:10381903
↑Ferec C, Raguenes O, Salomon R, Roche C, Bernard JP, Guillot M, Quere I, Faure C, Mercier B, Audrezet MP, Guillausseau PJ, Dupont C, Munnich A, Bignon JD, Le Bodic L. Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis. J Med Genet. 1999 Mar;36(3):228-32. PMID:10204851
↑Chen JM, Raguenes O, Ferec C, Deprez PH, Verellen-Dumoulin C. A CGC>CAT gene conversion-like event resulting in the R122H mutation in the cationic trypsinogen gene and its implication in the genotyping of pancreatitis. J Med Genet. 2000 Nov;37(11):E36. PMID:11073545
↑Pfutzer R, Myers E, Applebaum-Shapiro S, Finch R, Ellis I, Neoptolemos J, Kant JA, Whitcomb DC. Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis. Gut. 2002 Feb;50(2):271-2. PMID:11788572
↑Teich N, Le Marechal C, Kukor Z, Caca K, Witzigmann H, Chen JM, Toth M, Mossner J, Keim V, Ferec C, Sahin-Toth M. Interaction between trypsinogen isoforms in genetically determined pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of anionic trypsinogen (PRSS2). Hum Mutat. 2004 Jan;23(1):22-31. PMID:14695529 doi:10.1002/humu.10285
↑Teich N, Nemoda Z, Kohler H, Heinritz W, Mossner J, Keim V, Sahin-Toth M. Gene conversion between functional trypsinogen genes PRSS1 and PRSS2 associated with chronic pancreatitis in a six-year-old girl. Hum Mutat. 2005 Apr;25(4):343-7. PMID:15776435 doi:10.1002/humu.20148
↑Koshikawa N, Yasumitsu H, Nagashima Y, Umeda M, Miyazaki K. Identification of one- and two-chain forms of trypsinogen 1 produced by a human gastric adenocarcinoma cell line. Biochem J. 1994 Oct 1;303 ( Pt 1):187-90. PMID:7945238
↑Gaboriaud C, Serre L, Guy-Crotte O, Forest E, Fontecilla-Camps JC. Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151. J Mol Biol. 1996 Jun 28;259(5):995-1010. PMID:8683601 doi:10.1006/jmbi.1996.0376
