Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 2 of 2

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Two Crystal Structures Of Dihydrofolate Reductase-Thymidylate Synthase From Cryptosporidium Hominis Reveal Protein–Ligand Interactions Including A Structural Basis For Observed Antifolate Resistance, Amy C. Anderson Feb 2005

Two Crystal Structures Of Dihydrofolate Reductase-Thymidylate Synthase From Cryptosporidium Hominis Reveal Protein–Ligand Interactions Including A Structural Basis For Observed Antifolate Resistance, Amy C. Anderson

Open Dartmouth: Faculty Open Access Scholarship

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 ...


Arsenite Regulates Cystic Fibrosis Transmem­Brane Conductance Regulator And P-Glycoprotein: Evidence Of Pathway Independence, Rangan Maitra, Joshua Hamilton Jan 2005

Arsenite Regulates Cystic Fibrosis Transmem­Brane Conductance Regulator And P-Glycoprotein: Evidence Of Pathway Independence, Rangan Maitra, Joshua Hamilton

Open Dartmouth: Faculty Open Access Scholarship

In the past, people have argued for and against the theory of reciprocal regulation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and P-glycoprotein (Pgp). Data have indicated that this may occur in vitro during drug-induced selection of cells, and in vivo during development. Much of this debate has been caused by a severe lack of mechanistic details involved in such regulation. Our past data indicate that certain Pgp modulators can affect CFTR expression and function. The goal of this study was to investigate the effects of trivalent arsenic (arsenite), a known transcriptional activator of Pgp, on CFTR expression. In ...