1. Volume 119, Issue 3, Pages 615-623 (September 2000)
SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis 
Roland H. Pfützer, M.Michael Barmada, Andrew P.J. Brunskill, Robert Finch, P.Suzanne Hart, John Neoptolemos, William F. Furey, David C. Whitcomb 
Gastroenterology 
Volume 119, Issue 3, Pages (September 2000)
DOI: /gast
Copyright © 2000 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Comparison of human,40 porcine (data from Hecht et al.31), and rat41 (GenBank accession no. M27883) SPINK1/PSTI. Exons are based on comparison of human SPINK1 with draft DNA sequence from GenBank accession no. NM_ Obs var; observed variations in human protein sequence deduced from allele polymorphisms. Bold type shows the position of N34S variant (changes human sequence to porcine sequence22). Asterisk shows the “bait” lysine (K) in human and porcine, and arginine (R) in rat that projects into the specificity pocket of trypsin during trypsin inhibition. Note that the homology between human and porcine SPINK1 (PSTI) is 39 of 56 amino acids (71%, see peptides 1, 3, 4, 8, 9, 10, 11, 13, 14, 17, 21, 29, 32, 39, 42, 47, and 48), and human and rat SPINK1 (reported as rat PSTI -II41) is 36 of 56 amino acids (64%). Rat PSTI-I is monitor peptide.
Gastroenterology  , DOI: ( /gast )
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3. Fig. 2
Cumulative incidence of chronic pancreatitis in patients with SPINK1 mutations vs. patients without SPINK1 mutations. All patients are also PRSS1 (cationic trypsinogen) mutation negative. The vertical line at age 20 indicates the cutoff used for contingency table analysis. At this point 21 of 24 (87.5%) SPINK1 N34S mutation carriers had already developed symptoms of pancreatitis as compared with 41 of 64 (64.1%) nonmutation carriers.
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Superposition of the porcine SPINK1 structure (blue) on the human (modified for chymotrypsin specificity) SPINK1 structure (red). The main chain is shown as a ribbon diagram, whereas selected side chains are shown in a ball and stick representation. The flipping of side chains is apparent by comparing residues 33 and 34 in the 2 structures. Also shown are the target residue for cleavage (41) and the mutation site at residue 55 (codon numbering). The image was created with the program RIBBONS.42
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Tentative model for the human trypsin (yellow) human SPINK1 (red) complex. The main chain is shown as a ribbon diagram and selected side chains are shown in a ball and stick representation. The orientation is similar to that in Figure 3. Note the proximity of the binding loop (N34-Y41) and P55 to the enzyme. Y41 (K41 in wild-type SPINK1) is shown penetrating the enzyme's specificity pocket. The image was created with the program RIBBONS.42
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions