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1cgj

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Revision as of 14:54, 10 September 2015

THREE-DIMENSIONAL STRUCTURE OF THE COMPLEXES BETWEEN BOVINE CHYMOTRYPSINOGEN*A AND TWO RECOMBINANT VARIANTS OF HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR (KAZAL-TYPE)

Structural highlights

1cgj is a 2 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

Variants of the human pancreatic secretory trypsin inhibitor (PSTI) have been created during a protein design project to generate a high-affinity inhibitor with respect to some serine proteases other than trypsin. Two modified versions of human PSTI with high affinity for chymotrypsin were crystallized as a complex with chymotrypsinogen. Both crystallize isomorphously in space group P4(1)2(1)2 with lattice constants a = 84.4 A, c = 86.7 A and diffract to 2.3 A resolution. The structure was solved by molecular replacement. The final R-value after refinement with 8.0 to 2.3 A resolution data was 19.5% for both complexes after inclusion of about 50 bound water molecules. The overall three-dimensional structure of PSTI is similar to the structure of porcine PSTI in the trypsinogen complex (1TGS). Small differences in the relative orientation of the binding loop and the core of the inhibitors indicate flexible adaptation to the proteases. The chymotrypsinogen part of the complex is similar to chymotrypsin. After refolding induced by binding of the inhibitor the root-mean-square difference of the active site residues A186 to A195 and A217 to A222 compared to chymotrypsin was 0.26 A.

Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type).,Hecht HJ, Szardenings M, Collins J, Schomburg D J Mol Biol. 1991 Aug 5;220(3):711-22. PMID:1870127^[6]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Hecht HJ, Szardenings M, Collins J, Schomburg D. Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type). J Mol Biol. 1991 Aug 5;220(3):711-22. PMID:1870127

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1cgj"

@@ Line 2: / Line 2: @@
 <StructureSection load='1cgj' size='340' side='right' caption='[[1cgj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1cgj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CGJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1cgj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CGJ FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cgj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1cgj RCSB], [http://www.ebi.ac.uk/pdbsum/1cgj PDBsum]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cgj OCA], [http://pdbe.org/1cgj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1cgj RCSB], [http://www.ebi.ac.uk/pdbsum/1cgj PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1cgj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Bos taurus]]
+[[Category: Bovin]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Collins, J]]
 [[Category: Hecht, H J]]

1cgj

From Proteopedia

Revision as of 14:54, 10 September 2015

THREE-DIMENSIONAL STRUCTURE OF THE COMPLEXES BETWEEN BOVINE CHYMOTRYPSINOGEN*A AND TWO RECOMBINANT VARIANTS OF HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR (KAZAL-TYPE)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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