The crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveals a novel architecture for the bifunctional enzyme.
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چکیده
منابع مشابه
Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase.
We have determined the crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that has extensive interactions with the opposite DHFR-TS monomer of the homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis and of previously solved structures of DHFR-TS from ...
متن کاملDisruption of the crossover helix impairs dihydrofolate reductase activity in the bifunctional enzyme TS-DHFR from Cryptosporidium hominis.
In contrast with most species, including humans, which have monofunctional forms of the folate biosynthetic enzymes TS (thymidylate synthase) and DHFR (dihydrofolate reductase), several pathogenic protozoal parasites, including Cryptosporidium hominis, contain a bifunctional form of the enzymes on a single polypeptide chain having both catalytic activities. The crystal structure of the bifuncti...
متن کاملHighly efficient ligands for dihydrofolate reductase from Cryptosporidium hominis and Toxoplasma gondii inspired by structural analysis.
The search for effective therapeutics for cryptosporidiosis and toxoplasmosis has led to the discovery of novel inhibitors of dihydrofolate reductase (DHFR) that possess high ligand efficiency: compounds with high potency and low molecular weight. Detailed analysis of the crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis and a homology model of DHFR ...
متن کاملConstruction of a homodimeric dihydrofolate reductase-thymidylate synthase bifunctional enzyme.
A gene encoding a bifunctional homodimeric dihydrofolate reductase-thymidylate synthase (DHFR-TS) was constructed by destroying the stop codon of Escherichia coli dihydrofolate reductase (DHFR) and joining the coding sequences of the monofunctional enzymes by a five amino acid linker. The protein was designed to mimic features of active site proximity and electrostatics in the protozoan DHFR-TS...
متن کاملThe bifunctional dihydrofolate reductase thymidylate synthase of Tetrahymena thermophila provides a tool for molecular and biotechnology applications
BACKGROUND Dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are crucial enzymes in DNA synthesis. In alveolata both enzymes are expressed as one bifunctional enzyme. RESULTS Loss of this essential enzyme activities after successful allelic assortment of knock out alleles yields an auxotrophic marker in ciliates. Here the cloning, characterisation and functional analysis of Tetrahy...
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ورودعنوان ژورنال:
- The Journal of eukaryotic microbiology
دوره 50 Suppl شماره
صفحات -
تاریخ انتشار 2003