1y3f › Citations

Role of the intramolecular hydrogen bond network in the inhibitory power of chymotrypsin inhibitor 2.

Radisky ES, Lu CJ, Kwan G, Koshland DE
Biochemistry 44 6823-30 (2005)
Related entries: 1y1k, 1y33, 1y34, 1y3b, 1y3c, 1y3d, 1y48, 1y4a, 1y4d

Cited: 23 times
EuropePMC logo PMID: 15865427

Abstract

A series of mutants of chymotrypsin inhibitor 2 (CI2), at residues involved in intramolecular interactions that shape and constrain the binding loop, were studied to determine their relative importance for inhibition of the serine protease subtilisin BPN', and for resistance of the inhibitor to proteolysis. These functional properties were investigated in tandem with the crystal structures of the mutant inhibitor-enzyme complexes. A dense hydrogen bonding network that supports the binding loop in the vicinity of the scissile bond was found to be important both for enzyme affinity and for stability to proteolysis. Structural analysis, in combination with biochemical measurements, allows differentiation of the structural components most important for resistance to proteolysis and/or binding. The most critical participating residues in the network were found to be Thr-58, Glu-60, Arg-65, and Gly-83. Glu-60 is more important for resistance to proteolysis than for binding, while Arg-65 and two other Arg residues play a greater role in binding than in resistance to proteolysis. Structural comparisons reveal a wide variety of subtle conformational changes in response to mutation, with built-in robustness in the hydrogen bond network, such that loss of one contact is compensated by other new contacts.

Articles - 1y3f mentioned but not cited (1)

  1. From thiol-subtilisin to omniligase: Design and structure of a broadly applicable peptide ligase. Toplak A, Teixeira de Oliveira EF, Schmidt M, Rozeboom HJ, Wijma HJ, Meekels LKM, de Visser R, Janssen DB, Nuijens T. Comput Struct Biotechnol J 19 1277-1287 (2021)


Reviews citing this publication (1)

  1. Challenges in the use of sortase and other peptide ligases for site-specific protein modification. Morgan HE, Turnbull WB, Webb ME. Chem Soc Rev 51 4121-4145 (2022)

Articles citing this publication (21)

  1. Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Hu L, Li Z, Cheng J, Rao Q, Gong W, Liu M, Shi YG, Zhu J, Wang P, Xu Y. Cell 155 1545-1555 (2013)
  2. SKEMPI: a Structural Kinetic and Energetic database of Mutant Protein Interactions and its use in empirical models. Moal IH, Fernández-Recio J. Bioinformatics 28 2600-2607 (2012)
  3. Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure. Batra J, Robinson J, Soares AS, Fields AP, Radisky DC, Radisky ES. J Biol Chem 287 15935-15946 (2012)
  4. Determinants of affinity and proteolytic stability in interactions of Kunitz family protease inhibitors with mesotrypsin. Salameh MA, Soares AS, Navaneetham D, Sinha D, Walsh PN, Radisky ES. J Biol Chem 285 36884-36896 (2010)
  5. Long-range electrostatic complementarity governs substrate recognition by human chymotrypsin C, a key regulator of digestive enzyme activation. Batra J, Szabó A, Caulfield TR, Soares AS, Sahin-Tóth M, Radisky ES. J Biol Chem 288 9848-9859 (2013)
  6. A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior. Kromann-Hansen T, Oldenburg E, Yung KW, Ghassabeh GH, Muyldermans S, Declerck PJ, Huang M, Andreasen PA, Ngo JC. J Biol Chem 291 15156-15168 (2016)
  7. Rigidification of a flexible protease inhibitor variant upon binding to trypsin. Hanson WM, Domek GJ, Horvath MP, Goldenberg DP. J Mol Biol 366 230-243 (2007)
  8. Functional and structural roles of the Cys14-Cys38 disulfide of bovine pancreatic trypsin inhibitor. Zakharova E, Horvath MP, Goldenberg DP. J Mol Biol 382 998-1013 (2008)
  9. Engineering protein assemblies with allosteric control via monomer fold-switching. Campos LA, Sharma R, Alvira S, Ruiz FM, Ibarra-Molero B, Sadqi M, Alfonso C, Rivas G, Sanchez-Ruiz JM, Romero Garrido A, Valpuesta JM, Muñoz V. Nat Commun 10 5703 (2019)
  10. Investigation of an anomalously accelerating substitution in the folding of a prototypical two-state protein. Lawrence C, Kuge J, Ahmad K, Plaxco KW. J Mol Biol 403 446-458 (2010)
  11. ECMIS: computational approach for the identification of hotspots at protein-protein interfaces. Shingate P, Manoharan M, Sukhwal A, Sowdhamini R. BMC Bioinformatics 15 303 (2014)
  12. Amide Rotation Hindrance Predicts Proteolytic Resistance of Cystine-Knot Peptides. Zhou Y, Xie D, Zhang Y. J Phys Chem Lett 7 1138-1142 (2016)
  13. Identification of critical amino acid residues for human iNOS functional activity. Naureckiene S, Kodangattil SR, Kaftan EJ, Jones PG, Kennedy JD, Rogers KE, Chanda PK. Protein J 27 309-318 (2008)
  14. Exploring the role of structure and dynamics in the function of chymotrypsin inhibitor 2. Whitley MJ, Lee AL. Proteins 79 916-924 (2011)
  15. Important roles of hydroxylic amino acid residues in the function of Bacillus subtilis adenylosuccinate lyase. Segall ML, Cashman MA, Colman RF. Protein Sci 16 441-448 (2007)
  16. Resisting degradation by human elastase: commonality of design features shared by 'canonical' plant and bacterial macrocyclic protease inhibitor scaffolds. Brauer AB, McBride JD, Kelly G, Matthews SJ, Leatherbarrow RJ. Bioorg Med Chem 15 4618-4628 (2007)
  17. Identification of a novel set of scaffolding residues that are instrumental for the inhibitory property of Kunitz (STI) inhibitors. Khamrui S, Majumder S, Dasgupta J, Dattagupta JK, Sen U. Protein Sci 19 593-602 (2010)
  18. Molecular insight into chymotrypsin inhibitor 2 resisting proteolytic degradation. Wei W, Chen Y, Xie D, Zhou Y. Phys Chem Chem Phys 21 5049-5058 (2019)
  19. X-ray structure analysis and characterization of AFUEI, an elastase inhibitor from Aspergillus fumigatus. Sakuma M, Imada K, Okumura Y, Uchiya K, Yamashita N, Ogawa K, Hijikata A, Shirai T, Homma M, Nikai T. J Biol Chem 288 17451-17459 (2013)
  20. Slow conformational changes in the rigid and highly stable chymotrypsin inhibitor 2. Gavrilov Y, Prestel A, Lindorff-Larsen K, Teilum K. Protein Sci 32 e4604 (2023)
  21. Crystal structure of a three-tetrad, parallel, K+-stabilized human telomeric G-quadruplex at 1.35 Å resolution. Chen EV, Nicoludis JM, Powell BM, Li KS, Yatsunyk LA. Acta Crystallogr F Struct Biol Commun 79 144-150 (2023)


Quick links