Crystal Structures of a Unique Thermal-Stable Thymidylate Synthase

Crystal Structures of a Unique Thermal-Stable Thymidylate Synthase from Bacillus ... San Francisco, California 94143-0448, and Department of Pharmaceu...
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Biochemistry 1998, 37, 14736-14747

Crystal Structures of a Unique Thermal-Stable Thymidylate Synthase from Bacillus subtilis†,‡ Thomas J. Stout,*,§ Ute Schellenberger,|| Daniel V. Santi,⊥ and Robert M. Stroud*,§ Departments of Biochemistry and Biophysics, School of Medicine, UniVersity of California, San Francisco, San Francisco, California 94143-0448, and Department of Pharmaceutical Chemistry, UniVersity of California, San Francisco, San Francisco, California 94143-0448 ReceiVed May 28, 1998; ReVised Manuscript ReceiVed July 15, 1998

ABSTRACT:

Unlike all other organisms studied to date, Bacillus subtilis expresses two different thymidylate synthases: bsTS-A and bsTS-B. bsTS-A displays enhanced enzymatic and structural thermal stability uncharacteristic of most TSs. Despite the high level of TS conservation across most species, bsTS-A shares low sequence identity (