A Hypothesized Mechanism for Chronic Pancreatitis Caused by the N34S Mutation of Serine Protease Inhibitor Kazal-Type 1 Based on Conformational Studies

References

• Weiss FU, Skube ME, Lerch MM. Chronic pancreatitis. Curr Opin Gastroenterol. 2018;34(5):322–329. doi:10.1097/MOG.0000000000000461
   PubMed Web of Science ®Google Scholar
• Whitcomb DC, Gorry MC, Preston RA, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet. 1996;14(2):141–145. doi:10.1038/ng1096-141
   PubMed Web of Science ®Google Scholar
• Teich N, Rosendahl J, Tóth M, Mössner J, Sahin-Tóth M. Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis. Hum Mutat. 2006;27(8):721–730. doi:10.1002/humu.20343
   PubMed Web of Science ®Google Scholar
• Witt H, Luck W, Hennies HC, et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet. 2000;25(2):213–216. doi:10.1038/76088
   PubMed Web of Science ®Google Scholar
• Pfützer RH, Barmada MM, Brunskill APJ, et al. SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis. Gastroenterology. 2000;119(3):615–623. doi:10.1053/gast.2000.18017
   PubMed Web of Science ®Google Scholar
• Aoun E, Chang -C-CH, Greer JB, Papachristou GI, Barmada MM, Whitcomb DC. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis. PLoS One. 2008;3(4):e2003. doi:10.1371/journal.pone.0002003
   PubMed Web of Science ®Google Scholar
• Boulling A, Chen JM, Callebaut I, Férec C. Is the SPINK1 p. Asn34Ser missense mutation per se the true culprit within its associated haplotype? Webmed Central Genet. 2012;3(2):WMC003084. doi:10.9754/journal.wmc.2012.003084
   Google Scholar
• Chen JM, Férec C. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2009;10(1):63–87. doi:10.1146/annurev-genom-082908-150009
   PubMedGoogle Scholar
• Valmu L, Paju A, Lempinen M, Kemppainen E, Stenman U-H. Application of proteomic technology in identifying pancreatic secretory trypsin inhibitor variants in urine of patients with pancreatitis. Clin Chem. 2006;52(1):73–81. doi:10.1373/clinchem.2005.056861
   PubMed Web of Science ®Google Scholar
• Kuwata K, Hirota M, Ogawa M. Functional analysis of pancreatic secretory trypsin inhibitor protein with amino acid substitution. Int Congr Ser. 2003;1255(C):193–196. doi:10.1016/S0531-5131(03)00201-2
   Google Scholar
• Kiraly O, Wartmann T, Sahin-Toth M. Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation. Gut. 2007;56(10):1433–1438. doi:10.1136/gut.2006.115725
   PubMed Web of Science ®Google Scholar
• Boulling A, Le Maréchal C, Trouvé P, Raguénès O, Chen J-M J-M, Férec C. Functional analysis of pancreatitis-associated missense mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. Eur J Hum Genet. 2007;15(9):936–942. doi:10.1038/sj.ejhg.5201873
   PubMed Web of Science ®Google Scholar
• Kereszturi E, Kiraly O, Sahin-Toth M. Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut. 2009;58(4):545–549. doi:10.1136/gut.2008.164947
   PubMed Web of Science ®Google Scholar
• Shimosegawa T, Kume K, Masamune A. SPINK1, ADH2, and ALDH2 gene variants and alcoholic chronic pancreatitis in Japan. J Gastroenterol Hepatol. 2008;23(s1):S82–S86. doi:10.1111/j.1440-1746.2007.05291.x
   PubMedGoogle Scholar
• Sandhu B, Vitazka P, Ferreira-Gonzalez A, et al. Presence of SPINK-1 variant alters the course of chronic pancreatitis. J Gastroenterol Hepatol. 2011;26(6):965–969. doi:10.1111/j.1440-1746.2011.06713.x
   PubMed Web of Science ®Google Scholar
• Boulling A, Masson E, Zou W, et al. Identification of a functional enhancer variant within the chronic pancreatitis‐associated SPINK1 c.101A>G (p.Asn34Ser)‐containing haplotype. Hum Mutat. 2017;38(8):1014–1024. doi:10.1002/humu.23269
   PubMed Web of Science ®Google Scholar
• Threadgold J. The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease. Gut. 2002;50(5):675–681. doi:10.1136/gut.50.5.675
   PubMed Web of Science ®Google Scholar
• Drenth JPH. Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis. Gut. 2002;50(5):687–692. doi:10.1136/gut.50.5.687
   PubMed Web of Science ®Google Scholar
• Rai P, Sharma A, Gupta A, Aggarwal R. Frequency of SPINK1 N34S mutation in acute and recurrent acute pancreatitis. J Hepatobiliary Pancreat Sci. 2014;21(9):663–668. doi:10.1002/jhbp.111
   PubMed Web of Science ®Google Scholar
• Buchholz I, Nagel F, Klein A, et al. The impact of physiological stress conditions on protein structure and trypsin inhibition of serine protease inhibitor Kazal type 1 (SPINK1) and its N34S variant. Biochim Biophys Acta. 2020;1868(1):140281. doi:10.1016/j.bbapap.2019.140281
   Web of Science ®Google Scholar
• Sun Z, Kolssváry I, Kozakov D, Sahin-Tóth M, Vajda S. The N34S mutation of SPINK1 may impact the kinetics of trypsinogen activation to cause early trypsin release in the pancreas. bioRxiv. 2020;1–23. doi:10.1101/2020.08.21.262162
   Google Scholar
• Gaboriaud C, Serre L, Guy-Crotte O, Forest E, Fontecilla-Camps J-C. Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151. J Mol Biol. 1996;259(5):995–1010. doi:10.1006/jmbi.1996.0376
   PubMed Web of Science ®Google Scholar
• 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;220(3):711–722. doi:10.1016/0022-2836(91)90112-J
   PubMed Web of Science ®Google Scholar
• Anandakrishnan R, Aguilar B, Onufriev AV. H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations. Nucleic Acids Res. 2012;40(W1):W537–W541. doi:10.1093/nar/gks375
   PubMed Web of Science ®Google Scholar
• Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C. ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput. 2015;11(8):3696–3713. doi:10.1021/acs.jctc.5b00255
   PubMed Web of Science ®Google Scholar
• Abraham MJ, Murtola T, Schulz R, et al. Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1–2:19–25. doi:10.1016/j.softx.2015.06.001
   Google Scholar
• Khoury GA, Thompson JP, Smadbeck J, Kieslich CA, Floudas CA. Forcefield_PTM: Ab Initio Charge and AMBER forcefield parameters for frequently occurring post-translational modifications. J Chem Theory Comput. 2013;9(12):5653–5674. doi:10.1021/ct400556v
   PubMed Web of Science ®Google Scholar
• Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79(2):926–935. doi:10.1063/1.445869
   Web of Science ®Google Scholar
• Basconi JE, Shirts MR. Effects of temperature control algorithms on transport properties and kinetics in molecular dynamics simulations. J Chem Theory Comput. 2013;9(7):2887–2899. doi:10.1021/ct400109a
   PubMed Web of Science ®Google Scholar
• Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81(8):3684–3690. doi:10.1063/1.448118
   Web of Science ®Google Scholar
• Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: a linear constraint solver for molecular simulations. J Comput Chem. 1997;18(12):1463–1472. doi:10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
   Web of Science ®Google Scholar
• Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 03, Revision C. 02. Wallingford CT: Gaussian Inc; 2004.
   Google Scholar
• Humphrey W, Dalke A, Schulten K. VMD ‐ visual molecular dynamics. J Mol Graph. 1996;14(1):33–38. doi:10.1016/0263-7855(96)00018-5
   PubMedGoogle Scholar
• Roe DR, Cheatham TE. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–3095. doi:10.1021/ct400341p
   PubMed Web of Science ®Google Scholar
• Geist N, Kulke M, Schulig L, Link A, Langel W. Replica-based protein structure sampling methods II: advanced hybrid solvent TIGER2hs. J Phys Chem B. 2019;123(28):5995–6006. doi:10.1021/acs.jpcb.9b03134
   PubMed Web of Science ®Google Scholar
• Phillips JC, Braun R, Wang W, et al. Scalable molecular dynamics with NAMD. J Comput Chem. 2005;26(16):1781–1802. doi:10.1002/jcc.20289
   PubMed Web of Science ®Google Scholar
• Case DA, Betz R, Botello-Smith W, et al. AMBER 2016. San Francisco: University of California; 2016. doi:10.1021/ct200909j
   Google Scholar
• Hopkins CW, Le Grand S, Walker RC, Roitberg AE. Long-time-step molecular dynamics through hydrogen mass repartitioning. J Chem Theory Comput. 2015;11(4):1864–1874. doi:10.1021/ct5010406
   PubMed Web of Science ®Google Scholar
• Andersen HC. Rattle: a “velocity” version of the shake algorithm for molecular dynamics calculations. J Comput Phys. 1983;52(1):24–34. doi:10.1016/0021-9991(83)90014-1
   Web of Science ®Google Scholar
• Grest GS, Kremer K. Molecular dynamics simulation for polymers in the presence of a heat bath. Phys Rev A. 1986;33(5):3628–3631. doi:10.1103/PhysRevA.33.3628
   PubMed Web of Science ®Google Scholar
• Feller SE, Zhang Y, Pastor RW, Brooks BR. Constant pressure molecular dynamics simulation: the Langevin piston method. J Chem Phys. 1995;103(11):4613–4621. doi:10.1063/1.470648
   Web of Science ®Google Scholar
• Kulke M, Geist N, Möller D, Langel W. Replica-based protein structure sampling methods: compromising between explicit and implicit solvents. J Phys Chem B. 2018;122(29):7295–7307. doi:10.1021/acs.jpcb.8b05178
   PubMed Web of Science ®Google Scholar
• Nguyen H, Roe DR, Simmerling C. Improved generalized born solvent model parameters for protein simulations. J Chem Theory Comput. 2013;9(4):2020–2034. doi:10.1021/ct3010485
   PubMed Web of Science ®Google Scholar
• Eastman P, Swails J, Chodera JD, et al. OpenMM 7: rapid development of high performance algorithms for molecular dynamics. PLOS Comput Biol. 2017;13(7):e1005659. doi:10.1371/journal.pcbi.1005659
   PubMed Web of Science ®Google Scholar
• Li X, Latour RA, Stuart SJ. TIGER2: an improved algorithm for temperature intervals with global exchange of replicas. J Chem Phys. 2009;130(17):174106. doi:10.1063/1.3129342
   PubMed Web of Science ®Google Scholar
• Kästner J. Umbrella sampling. Wiley Interdiscip Rev Comput Mol Sci. 2011;1(6):932–942. doi:10.1002/wcms.66
   Web of Science ®Google Scholar
• Bauer D. WHM v1.0.0; 2020. Available from: https://github.com/danijoo/WHAM. Accessed April 23, 2021.
   Google Scholar
• Sahin-Tóth M, Kukor Z, Nemoda Z. Human cationic trypsinogen is sulfated on Tyr154. FEBS J. 2006;273(22):5044–5050. doi:10.1111/j.1742-4658.2006.05501.x
   PubMed Web of Science ®Google Scholar
• Ju T, Niu W, Cerny R, Bollman J, Roy A, Guo J. Molecular recognition of sulfotyrosine and phosphotyrosine by the Src homology 2 domain. Mol Biosyst. 2013;9(7):1829. doi:10.1039/c3mb70061e
   PubMedGoogle Scholar
• Kereszturi É, Sahin-Tóth M. Pancreatic cancer cell lines heterozygous for the SPINK1 p.N34S haplotype exhibit diminished expression of the variant allele. Pancreas. 2017;46(6):e54–e55. doi:10.1097/MPA.0000000000000817
   PubMed Web of Science ®Google Scholar
• Szabó A, Toldi V, Gazda LD, Demcsák A, Tőzsér J, Sahin-Tóth M. Defective binding of SPINK1 variants is an uncommon mechanism for impaired trypsin inhibition in chronic pancreatitis. J Biol Chem. 2021;296:100343. doi:10.1016/j.jbc.2021.100343
   PubMed Web of Science ®Google Scholar
• Kuwata K, Hirota M, Shimizu H, et al. Functional analysis of recombinant pancreatic secretory trypsin inhibitor protein with amino-acid substitution. J Gastroenterol. 2002;37(11):928–934. doi:10.1007/s005350200156
   PubMed Web of Science ®Google Scholar