A PLASMID-ENCODED DIHYDROFOLATE-REDUCTASE FROM TRIMETHOPRIM-RESISTANTBACTERIA HAS A NOVEL D-2-SYMMETRICAL ACTIVE-SITE

Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 D HFR) exhibit high-level resistance to the antibiotic trimethoprim. Nat ive R67 DHFR is a 34,000 M(r) homotetramer which exists in equilibrium with an inactive dimeric form. The structure of native R67 DHFR has n ow been solved at 1.7 Angstrom resolution and is unrelated to that of chromosomal DHFR, Homotetrameric R67 DHFR has an unusual pore, 25 Angs trom in length, passing through the middle of the molecule. Two folate molecules bind asymmetrically within the pore indicating that the enz yme's active site consists of symmetry related binding surfaces from a ll four identical units.