4FGT

Allosteric peptidic inhibitor of human thymidylate synthase that stabilizes inactive conformation of the enzyme.

Summary for 4FGT

• Entry DOI: 10.2210/pdb4fgt/pdb
• Related: 3EGY 3N5E
• Descriptor: Thymidylate synthase, CG peptide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: dimer, mutant k47a of hts, inactive hts conformation, hts complex with peptidic inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P04818
• Total number of polymer chains: 2
• Total formula weight: 38076.39

Authors

Tochowicz, A.,Finer-Moore, J.,Stroud, R.M.,Costi, M.P. (deposition date: 2012-06-04, release date: 2013-03-06, Last modification date: 2024-11-27)

Primary citation

Tochowicz, A.,Santucci, M.,Saxena, P.,Guaitoli, G.,Trande, M.,Finer-Moore, J.,Stroud, R.M.,Costi, M.P.
Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.
J.Med.Chem., 58:1012-1018, 2015

PubMed 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.

PubMed: 25427005
DOI: 10.1021/jm5011176

Experimental method

X-RAY DIFFRACTION (2 Å)