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DESIGN AND STRUCTURES OF DISULFIDE CONTAINING SUBTILISIN VARIANTS

Katz, Bradley A.
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Issue Date
1989
Submitted date
2023-11-03
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Abstract
The crystal structures of 4 variants of subtilisin, each one containing an engineered disulfide crosslink have been determined. The geometries of the engineered disulfide groups are atypical. For the Cys24-Cys87 and Cys22-Cys87 disulfides there is a relationship between their measured redox potentials and their calculated dihedral energies. Disulfide introduction produced cavities in the protein structures. The cavity produced by removal of Met119 in A29C/M119C (Ala29 to Cys, Met119 to Cys) was partially filled by a disordering of nearby Asn117. The cavities were often filled with ordered water molecules that replaced interactions of the removed groups. Molecular modelling provided insight into the location where a disulfide could be incorporated, and into its resulting geometry. The structures of A29C/M119C and of V26C/A232C showed that introduction of disulfides into buried hydrophobic regions resulted in long range concerted rearrangements.
Citation
Advances in protein design, 127 - 136
Affiliation
Department of Pharmaceutical Chemistry University of California, San Francisco San Francisco, California 94143 Department of Biomolecular Chemistry Genentech Inc. 460 Point San Bruno Blvd South San Francisco, California 94080 and Research Department Genencor, Inc. 180 Kimball Way South San Francisco, California 94080 present address: Triton Biosciences Inc. 1501 Harbor Bay Parkway Alameda, California 94501
Publisher
GBF Gesellschaft für Biotechnologische Forschung mbH, Braunschweig
Journal
Advances in protein design, 1988
URI
http://hdl.handle.net/10033/623528
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Book chapter
conference paper
Language
en
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Series/Report no.
GBF monographs ; Volume 12
ISSN
0930-4320
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ISBN
3527280243
0895739534
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License
Attribution-NonCommercial-ShareAlike 4.0 International
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