Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of F22A, Y23A, N43G, and F45A.
Crystal structures of four mutants of bovine pancreatic trypsin inhibitor (F22A, Y23A, N43G, and F45A), engineered to alter their stability properties, have been determined. The mutated residues, which are highly conserved among Kunitz-type inhibitors, are located in the rigid core of the molecule. Replacement of the partially buried bulky residues of the wild-type protein with smaller residues resulted in crevices open to the exterior of the molecule. The overall three-dimensional structure of these mutants is very similar to that of the wild-type protein and only small rearrangements are observed among the atoms lining the crevices.
Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL, Basic Research Program, Maryland 21702.
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Danishefsky
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D
Housset
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KS
Kim
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F
Tao
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J
Fuchs
C
C
Woodward
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A
Wlodawer
D000818:Animals; D002417:Cattle; D006860:Hydrogen Bonding; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010179:Pancreas; D017433:Protein Structure, Secondary; D014361:Trypsin Inhibitors / Q000737:chemistry* / Q000235:genetics*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D014361:Trypsin Inhibitors; D014867:Water