Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance

Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Amy C Anderson

Abstract

Cryptosporidium hominis is a protozoan parasite that causes acute gastrointestinal 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 A 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.

References

Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S PetersonT E Wellems
Jun 1, 1988·European Journal of Biochemistry·C OefnerF K Winkler
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·W SirawarapornD V Santi
Jan 1, 1997·Emerging Infectious Diseases·R L Guerrant
Apr 29, 1998·Advances in Parasitology·S Tzipori
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Apr 22, 2003·Nature Structural Biology·Jirundon YuvaniyamaYongyuth Yuthavong
May 26, 2004·Acta Crystallographica. Section D, Biological Crystallography·Ryan H LilienBruce R Donald

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Citations

Nov 15, 2008·Journal of Medicinal Chemistry·Jennifer M BeierleinAmy C Anderson
Jan 27, 2009·Eukaryotic Cell·Jieying LiuAmy C Anderson
Feb 4, 2009·Experimental Parasitology·Stanley Dean Rider, Guan Zhu
Nov 25, 2014·Biophysical Journal·Vincent T MetzgerJ Andrew McCammon
Dec 15, 2010·Trends in Parasitology·Stacy S Hung, John Parkinson
May 25, 2016·Biochimica Et Biophysica Acta. General Subjects·Kinga Nyíri, Beáta G Vértessy
Apr 1, 2014·Parasitology·Matthias Lendner, Arwid Daugschies
Jun 6, 2006·Bioorganic & Medicinal Chemistry Letters·Veljko M PopovAmy C Anderson

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