Document Type
Article
Publication Date
2-8-2005
Publication Title
Acta Crystallographica. Section F - Structural Biology and Crystallization Communications
Department
Department of Chemistry
Abstract
Cryptosporidium hominis is a protozoan parasite that causes acute gastro- intestinal illness. There are no effective therapies for cryptosporidiosis, highlighting the need for new drug-lead discovery. An analysis of the protein ligand interactions in two crystal structures of dihydrofolate reductase- thymidylate synthase DHFR-TS) from C. hominis, determined at 2.8 and 2.87 AÊ resolution, reveals that the interactions of residues Ile29, Thr58 and Cys113 in the active site of C. hominis DHFR provide a possible structural basis for the observed antifolate resistance. A comparison with the structure of human DHFR reveals active-site differences that may be exploited for the design of species-selective inhibitors.
DOI
10.1107/S1744309105002435
Original Citation
Anderson AC. Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Mar 1;61(Pt 3):258-62. doi: 10.1107/S1744309105002435. Epub 2005 Feb 8. PMID: 16511011; PMCID: PMC1952288.
Dartmouth Digital Commons Citation
Anderson, Amy C., "Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein–ligand interactions including a structural basis for observed antifolate resistance" (2005). Dartmouth Scholarship. 421.
https://digitalcommons.dartmouth.edu/facoa/421
