TY - JOUR
T1 - Partially Folded Bovine Pancreatic Trypsin Inhibitor Analogues Attain Fully Native Structures when Co-Crystallized with S195A Rat Trypsin
AU - Getun, Irina V.
AU - Brown, C. Kent
AU - Tulla-Puche, Judit
AU - Ohlendorf, Douglas
AU - Woodward, Clare
AU - Barany, George
PY - 2008/1/18
Y1 - 2008/1/18
N2 - Crystal structures, at 1.7 Å resolution, were solved for complexes between each of two chemically synthesized partially folded analogues of bovine pancreatic trypsin inhibitor (BPTI) with the proteolytically inactive rat trypsin mutant S195A. The BPTI analogue termed [14-38]Abu retains only the disulfide bond between Cys14 and Cys38, while Cys5, Cys30, Cys51, and Cys55 are replaced by isosteric α-amino-n-butyric acid residues. The analogue K26P,A27D[14-38]Abu contains two further replacements, by statistically favored residues, in the type I β-turn that has been suggested to be a main site for initiation of BPTI folding. As a control, the structure of the complex between S195A trypsin and wild-type BPTI was also solved. Despite significant differences in the degree of structure detected among these three BPTIs in solution by several biophysical techniques, their tertiary folds once bound to S195A trypsin in a crystalline lattice are essentially superimposable.
AB - Crystal structures, at 1.7 Å resolution, were solved for complexes between each of two chemically synthesized partially folded analogues of bovine pancreatic trypsin inhibitor (BPTI) with the proteolytically inactive rat trypsin mutant S195A. The BPTI analogue termed [14-38]Abu retains only the disulfide bond between Cys14 and Cys38, while Cys5, Cys30, Cys51, and Cys55 are replaced by isosteric α-amino-n-butyric acid residues. The analogue K26P,A27D[14-38]Abu contains two further replacements, by statistically favored residues, in the type I β-turn that has been suggested to be a main site for initiation of BPTI folding. As a control, the structure of the complex between S195A trypsin and wild-type BPTI was also solved. Despite significant differences in the degree of structure detected among these three BPTIs in solution by several biophysical techniques, their tertiary folds once bound to S195A trypsin in a crystalline lattice are essentially superimposable.
KW - BPTI
KW - [14-38]
KW - crystal structure
KW - ligand-induced folding
KW - partially folded protein
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U2 - 10.1016/j.jmb.2007.10.084
DO - 10.1016/j.jmb.2007.10.084
M3 - Article
C2 - 18054043
AN - SCOPUS:37349114104
VL - 375
SP - 812
EP - 823
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 3
ER -