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.

Alanine Mutants of the Interface Residues of Human Thymidylate Synthase Decode Key Features of the Binding Mode of Allosteric Anticancer Peptides / Tochowicz, Anna Maria; Santucci, Matteo; Saxena, Puneet; Guaitoli, Giambattista; Costi, Maria Paola. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 58:2(2015), pp. 1012-1018. [10.1021/jm5011176]

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

TOCHOWICZ, Anna Maria;SANTUCCI, MATTEO;SAXENA, PUNEET;GUAITOLI, GIAMBATTISTA;COSTI, Maria Paola
2015

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.
2015
26-nov-2014
58
2
1012
1018
Alanine Mutants of the Interface Residues of Human Thymidylate Synthase Decode Key Features of the Binding Mode of Allosteric Anticancer Peptides / Tochowicz, Anna Maria; Santucci, Matteo; Saxena, Puneet; Guaitoli, Giambattista; Costi, Maria Paola. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 58:2(2015), pp. 1012-1018. [10.1021/jm5011176]
Tochowicz, Anna Maria; Santucci, Matteo; Saxena, Puneet; Guaitoli, Giambattista; Costi, Maria Paola
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1064103
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