Mutagenesis, structure and function studies of thymidylate synthase.
The mechanism and structure of thymidylate synthase (TS) are fairly well understood. The function of amino acid residues of the enzyme have been studied by "replacement set mutagenesis" where multiple mutations at a given residue are produced and studied in detail. Some surprising results are (a) that there are few truly essential amino acids in TS, (b) that water may play an important role as a general acid/base catalyst, and (c) that a single mutation of Asn 229 to Asp changes specificity from a dUMP methylase to a dCMP methylase. Other mutagenesis and structure-function studies of interest will be discussed.
Santi
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Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001665:Binding Sites; D002384:Catalysis; D004578:Electron Spin Resonance Spectroscopy; D016296:Mutagenesis; D010710:Phosphates / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014961:X-Ray Diffraction
D010710:Phosphates; D001224:Aspartic Acid; D001216:Asparagine; D013940:Thymidylate Synthase