1. Alanine Mutants of the Interface Residues of Human Thymidylate Synthase Decode Key Features of the Binding Mode of Allosteric Anticancer Peptides
- Author
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Janet Finer-Moore, Giambattista Guaitoli, Maria Paola Costi, Anna Tochowicz, Matteo Trande, Robert M. Stroud, Puneet Saxena, and Matteo Santucci
- Subjects
interface inhibitors ,Stereochemistry ,Allosteric regulation ,Mutant ,Antineoplastic Agents ,Peptide ,Crystallography, X-Ray ,Thymidylate synthase ,Article ,Structure-Activity Relationship ,Molecular recognition ,Allosteric Regulation ,Drug Discovery ,Medicine and Health Sciences ,Humans ,Structure–activity relationship ,Enzyme Inhibitors ,interface mutants ,chemistry.chemical_classification ,Alanine ,biology ,Thymidylate synthase, interface inhibitors, peptide inhibitors, site-directed mutageneisis, interface mutants ,Mutagenesis ,Thymidylate Synthase ,peptide inhibitors ,site-directed mutageneisis ,Biochemistry ,chemistry ,Mutagenesis, Site-Directed ,biology.protein ,Molecular Medicine - 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.
- Published
- 2014
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