The Crystal Structure of Dihydrofolate Reductase-Thymidylate Synthase from Cryptosporidium hominis Reveals a Novel Architecture for the Bifunctional Enzyme

Journal of Eukaryotic Microbiology

Volumn 50, Issue SUPPL., 2003, Pages 555-556

  O'Neil, Robert H ^a   Lilien, Ryan H ^b   Donald, Bruce R ^b   Stroud, Robert M ^c   Anderson, Amy C ^a  

^a Dartmouth College   (United States)

^b Dartmouth Department of Computer Science_Dartmouth College   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROFOLATE REDUCTASE; MULTIENZYME COMPLEX; THYMIDYLATE SYNTHASE; THYMIDYLATE SYNTHASE DIHYDROFOLATE REDUCTASE; THYMIDYLATE SYNTHASE-DIHYDROFOLATE REDUCTASE;

ENZYME;

ANIMAL; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; CONFERENCE PAPER; CRYPTOSPORIDIUM; ENZYMOLOGY; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

ANIMALS; CELL LINE; CRYPTOSPORIDIUM; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; MULTIENZYME COMPLEXES; PROTEIN CONFORMATION; TETRAHYDROFOLATE DEHYDROGENASE; THYMIDYLATE SYNTHASE;

ANIMALIA; CRYPTOSPORIDIUM; CRYPTOSPORIDIUM HOMINIS;

EID: 0346966128     PISSN: 10665234     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1550-7408.2003.tb00627.x     Document Type: Conference Paper

References (11)

1. Anderson, A., Perry, K., Freymann, D. & Stroud, R. 2000. The crystal structure of thymidylate synthase from Pneumocystis carinii reveals a fungal insert important for drug design. J. Mol. Biol., 297:645-657.
2. Anderson, A., O'Neil, R., Surti, T. & Stroud, R. 2001. Approaches to solving the rigid receptor problem by identifying a minimal set of flexible residues during ligand docking. Chem. Biol., 8:445-457.
3. Brunger, A. 1998. Crystallography and NMR system: a new software suite for macromolecular structure determination. Acta Cryst. D, 54:905-921.
4. Cody, V., Galitsky, N., Rak, D., Luft, J., Pangborn, W. & Queener, S. 1999. Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+. Biochemistry, 38:4303-4312.
5. Knighton, D., Kan, C., Howland, E., Janson, C., Hostomska, Z., Welsh, K. & Matthews, D. 1994. Structure of and kinetic channeling in bifunctional dihydrofolate reductase-thymidylate synthase. Nat. Struct. Biol., 1:186-194.
6. Montfort, W., Perry, K., Fauman, E., Finer-Moore, J., Maley, G., Hardy, L., Maley, F. & Stroud, R. 1990. Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate. Biochemistry, 29:6964-6977.
7. Nelson, R. & Rosowsky, A. 2001. Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: structure-activity and structure-selectivity correlations. Antimicrob. Agents Chemother., 45:3293-3303.
8. Oefner, C., D'Arcy, A. & Winkler, F. 1988. Crystal structure of human dihydrofolate reductase complexed with folate. Eur. J. Biochem., 174: 377-385.
9. Otwinowski, Z. 1993. DENZO 1-56-62. In: SERC Daresbury Laboratory; Warrington, U.K.
10. Vasquez, J., Gooze, L., Kim, K., Gut, J., Petersen, C. & Nelson, R. 1996. Potential antifolate resistance determinants and genotypic variation in the bifunctional dihydrofolate reductase-thymidylate synthase gene from human and bovine isolates of Cryptosporidium parvum. Mol. Biochem. Parasitol., 79:153-165.
11. Yuvaniyama, J., Chitnumsub, P., Kamchonwongpaisan, S., Vanichtanankul, J., Sirawaraporn, W., Taylor, P., Walkinshaw, M. & Yuthavong, Y. 2003. Insights into antifolate resistance from malarial DHFR-TS structures. Nat. Struct. Biol., 10:357-365.