Mechanism of protein folding. IV. Forming and breaking of disulfide bonds in bovine pancreatic tripsin inhibitor.

The folding mechanism of bovine pancreatic tripsin inhibitor (BPTI) is explained theoretically on the basis of the island model, where the driving force of folding is hydrophobic interaction. For this purpose, we take a look at the formation and breaking of disulfide bonds during the folding process of BPTI. The intermediate conformations and the native one are successfully obtained, which satisfy the so-called "lampshade" geometrical criterion for the formation of the disulfide bonds. The folding pathway is consistent with the renaturation experiment by Creighton. In addition, an elaborate treatment of side chains of amino acid residues by the software programme CHARMm confirms quantitatively the formation of disulfide bridges.

[1]  T. Creighton,et al.  The 5–55 single‐disulphide intermediate in folding of bovine pancreatic trypsin inhibitor , 1991, FEBS letters.

[2]  H. Bremermann.  A method of unconstrained global optimization , 1970 .

[3]  M. Yamamoto,et al.  Mechanism of protein folding: I. General considerations and refolding of myoglobin , 1988, Proteins.

[4]  M. Levitt,et al.  Refinement of protein conformations using a macromolecular energy minimization procedure. , 1969, Journal of molecular biology.

[5]  K. Watanabe,et al.  Mechanism of protein folding. III. Disulfide bonding. , 1991, Biophysical chemistry.

[6]  T. Creighton,et al.  The two-disulphide intermediates and the folding pathway of reduced pancreatic trypsin inhibitor. , 1975, Journal of molecular biology.

[7]  M. Aida,et al.  An ab initio MO study on the disulfide bond: properties concerning the characteristic S-S dihedral angle , 1986 .

[8]  I. Kuntz,et al.  Mutants of bovine pancreatic trypsin inhibitor lacking cysteines 14 and 38 can fold properly , 1987, Science.

[9]  H A Scheraga,et al.  Recent progress in the theoretical treatment of protein folding , 1983, Biopolymers.

[10]  N. Sait̂o.  Principles of protein architecture. , 1989, Advances in biophysics.

[11]  M. Levitt,et al.  Computer simulation of protein folding , 1975, Nature.

[12]  M. Laskowski,et al.  The basic trypsin inhibitor of bovine pancreas. VII. Reduction with borohydride of disulfide bond linking half-cystine residues 14 and 38. , 1967, The Journal of biological chemistry.

[13]  M. Karplus,et al.  CHARMM: A program for macromolecular energy, minimization, and dynamics calculations , 1983 .

[14]  T. Creighton,et al.  Kinetic role of a meta-stable native-like two-disulphide species in the folding transition of bovine pancreatic trypsin inhibitor. , 1984, Journal of molecular biology.

[15]  H. Scheraga,et al.  Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids , 1975 .

[16]  T. Creighton,et al.  Experimental studies of protein folding and unfolding. , 1978, Progress in biophysics and molecular biology.

[17]  T. Inoue,et al.  Mechanism of protein folding. II. Lysozyme and phospholipase. , 1991, Biophysical chemistry.

[18]  M. Levitt.  A simplified representation of protein conformations for rapid simulation of protein folding. , 1976, Journal of molecular biology.

[19]  H. Scheraga,et al.  Model of protein folding: inclusion of short-, medium-, and long-range interactions. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. S. Kim,et al.  Reexamination of the folding of BPTI: predominance of native intermediates , 1991, Science.

[21]  Terrence G. Oas,et al.  A peptide model of a protein folding intermediate , 1988, Nature.

[22]  J. Israelachvili,et al.  The hydrophobic interaction is long range, decaying exponentially with distance , 1982, Nature.

[23]  M Karplus,et al.  Conformations of intermediates in the folding of the pancreatic trypsin inhibitor. , 1987, Journal of molecular biology.

[24]  T. Creighton,et al.  Conformational restrictions on the pathway of folding and unfolding of the pancreatic trypsin inhibitor. , 1977, Journal of molecular biology.