1hpt

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THREE-DIMENSIONAL STRUCTURE OF A RECOMBINANT VARIANT OF HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR (KAZAL TYPE)

Structural highlights

1hpt is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ISK1_HUMAN Defects in SPINK1 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] Defects in SPINK1 are the cause of susceptibility to tropical calcific pancreatitis (TCP) [MIM:608189. TCP is an idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer.[4] [5]

Function

ISK1_HUMAN This is a trypsin inhibitor, its physiological function is to prevent the trypsin-catalyzed premature activation of zymogens within the pancreas.

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

A modified version of the human pancreatic trypsin inhibitor (PSTI), generated in a protein-design project, has been crystallized in spacegroup P4(3) with lattice constants a = 40.15 A, c = 33.91 A. The structure has been solved by molecular replacement. Refinement of the structure by simulated annealing and conventional restrained least-squares yielded for 8.0 to 2.3 A data a final R-value of 19.1%. Differences to the known structures of porcine PSTI complexed with trypsinogen and modified human PSTI complexed with chymotrypsinogen occur at the flexible N-terminal part of the molecule. These differences are influenced by crystal packing, as are low temperature factors for the binding loop. The geometry of the binding loop is similar to the complexed structures.

Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type).,Hecht HJ, Szardenings M, Collins J, Schomburg D J Mol Biol. 1992 Jun 20;225(4):1095-103. PMID:1613792[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, Landt O, Becker M. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet. 2000 Jun;25(2):213-6. PMID:10835640 doi:10.1038/76088
  2. Chen JM, Mercier B, Audrezet MP, Ferec C. Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis. J Med Genet. 2000 Jan;37(1):67-9. PMID:10691414
  3. Deybach JC, Phung L, Lamoril J, Bouizegarene P, Levy P, Deybach JC, Ruszniewski P. Gene symbol: Spink1-Omim 167790. Disease: Hereditary pancreatitis. Hum Genet. 2003 Sep;113(4):369. PMID:12974284
  4. Hassan Z, Mohan V, Ali L, Allotey R, Barakat K, Faruque MO, Deepa R, McDermott MF, Jackson AE, Cassell P, Curtis D, Gelding SV, Vijayaravaghan S, Gyr N, Whitcomb DC, Khan AK, Hitman GA. SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent. Am J Hum Genet. 2002 Oct;71(4):964-8. Epub 2002 Aug 16. PMID:12187509 doi:S0002-9297(07)60381-4
  5. Chandak GR, Idris MM, Reddy DN, Bhaskar S, Sriram PV, Singh L. Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. J Med Genet. 2002 May;39(5):347-51. PMID:12011155
  6. Hecht HJ, Szardenings M, Collins J, Schomburg D. Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (Kazal type). J Mol Biol. 1992 Jun 20;225(4):1095-103. PMID:1613792

Contents


PDB ID 1hpt

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