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Alanine Mutants of the Interface Residues of Human Thymidylate Synthase Decode Key Features of the Binding Mode of Allosteric Anticancer Peptides

By Anna Maria Tochowicz, Matteo Santucci, Puneet Saxena, Giambattista Guaitoli and Maria Paola Costi

Abstract

Allosteric peptide inhibitors of thymidylate synthase (hTS) bind to the dimer interface and stabilize the inactive form of the protein. Four interface residues were mutated to alanine, and interaction studies were employed to decode the key role of these residues in the peptide molecular recognition. This led to the identification of three crucial interface residues F59, L198, and Y202 that impart activity to the peptide inhibitors and suggest the binding area for further inhibitor design

Topics: Thymidylate synthase, interface inhibitors, peptide inhibitors, site-directed mutageneisis, interface mutants
Publisher: 'American Chemical Society (ACS)'
Year: 2015
DOI identifier: 10.1021/jm5011176
OAI identifier: oai:iris.unimore.it:11380/1064103
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