1SEJ

Crystal Structure of Dihydrofolate Reductase-Thymidylate Synthase from Cryptosporidium hominis Bound to 1843U89/NADPH/dUMP

Summary for 1SEJ

• Entry DOI: 10.2210/pdb1sej/pdb
• Related: 1qzf
• Descriptor: bifunctional dihydrofolate reductase-thymidylate synthase, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, S)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC ACID, ... (5 entities in total)
• Functional Keywords: bifunctional enzyme, transferase, oxidoreductase
• Biological source: Cryptosporidium hominis
• Total number of polymer chains: 5
• Total formula weight: 311585.64

Authors

Anderson, A.C. (deposition date: 2004-02-17, release date: 2004-05-18, Last modification date: 2023-08-23)

Primary citation

Anderson, A.C.
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, 61:258-262, 2005

PubMed 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.

PubMed: 16511011
DOI: 10.1107/S1744309105002435

Experimental method

X-RAY DIFFRACTION (2.87 Å)