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De novo designed polypeptide catalysts with adopted folded structures
Author(s) -
Baltzer Lars,
Broo Kerstin S.
Publication year - 1998
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1998)47:1<31::aid-bip5>3.0.co;2-y
Subject(s) - chemistry , catalysis , protonation , nucleophile , histidine , substrate (aquarium) , hydrolysis , aqueous solution , stereochemistry , transesterification , combinatorial chemistry , enzyme , organic chemistry , ion , oceanography , geology
Designed polypeptide catalysts have been shown to catalyze hydrolysis and transesterification reactions of p ‐nitrophenyl esters by a mechanism that includes the nucleophilic attack by an unprotonated histidine and general‐acid catalysis by a flanking protonated histidine. The catalysis is cooperative and exhibits rate enhancements of three orders of magnitude over that of the 4‐methylimidazole catalyzed reaction. Substrate recognition by residues introduced in the adjoining helix was demonstrated for the negatively charged substrate mono‐ p ‐nitrophenyl fumarate. The results have been compared to those obtained for other designed polypeptide catalysts with similar efficiency, and it was concluded that the hallmarks of naturally occurring biocatalysts have now been demonstrated in polypeptide catalyzed reactions, although with considerably less efficiency than native enzymes. It was found that so far the most severe limitation of folded polypeptide catalysts is the efficiency obtained in the bond‐making and bond‐breaking steps, whereas the binding of substrates, even on the surface of helical structures in aqueous solution, is of comparable strength to that which occurs in nature. © 1998 John Wiley & Sons, Inc. Biopoly 47: 31–40, 1998