Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs

• Published in: Journal of molecular biology Vol. 295; no. 2; pp. 307 - 323
• Main Authors: Li, Rongbao, Sirawaraporn, Rachada, Chitnumsub, Penchit, Sirawaraporn, Worachart, Wooden, Jason, Athappilly, Francis, Turley, Stewart, Hol, Wim G.J
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 14.01.2000
• Subjects: Amino Acid Sequence; antitubercular agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - pharmacology; Br-WR99210; dihydrofolate reductase; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Humans; methotrexate; Molecular Sequence Data; Mycobacterium tuberculosis; Mycobacterium tuberculosis - enzymology; NADP - metabolism; Protein Binding; Protein Conformation; Sequence Homology, Amino Acid; Tetrahydrofolate Dehydrogenase - chemistry; Tetrahydrofolate Dehydrogenase - metabolism; trimethoprim; DHFR; Mycobacterium tuberculosis; APS; trimethoprim; drug design; TMP; PYR; methotrexate; MDR; dihydrofolate reductase; TB

Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate and is essential for the synthesis of thymidylate, purines and several amino acids. Inhibition of the enzyme’s activity leads to arrest of DNA synthesis and cell death. The enzyme has been stu...