title: A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site.
abstract: Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 DHFR) exhibit high-level resistance to the antibiotic trimethoprim. Native 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 now been solved at 1.7 A resolution and is unrelated to that of chromosomal DHFR. Homotetrameric R67 DHFR has an unusual pore, 25 A in length, passing through the middle of the molecule. Two folate molecules bind asymmetrically within the pore indicating that the enzyme's active site consists of symmetry related binding surfaces from all four identical units.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093, USA.
authors.forename: N
authors.initials: N
authors.lastname: Narayana
authors.forename: D A
authors.initials: DA
authors.lastname: Matthews
authors.forename: E E
authors.initials: EE
authors.lastname: Howell
authors.forename: X
authors.initials: X
authors.lastname: Nguyen-huu
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000235:genetics*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000235:genetics; D014295:Trimethoprim / Q000737:chemistry / Q000378:metabolism; D014296:Trimethoprim Resistance / Q000235:genetics*
chemical_list: D005493:Folic Acid Antagonists; D011994:Recombinant Proteins; D009249:NADP; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase