3VCO

Schistosoma mansoni Dihydrofolate reductase

Summary for 3VCO

• Entry DOI: 10.2210/pdb3vco/pdb
• Descriptor: Dihydrofolate reductase, SULFATE ION (3 entities in total)
• Functional Keywords: reductase, oxidoreductase
• Biological source: Schistosoma mansoni (Blood fluke)
• Total number of polymer chains: 1
• Total formula weight: 22968.26

Authors

Serrao, V.H.B.,Romanello, L.,Cassago, A.,DeMarco, R.,Pereira, H.M. (deposition date: 2012-01-04, release date: 2013-03-06, Last modification date: 2023-09-13)

Primary citation

Serrao, V.H.B.,Romanello, L.,Cassago, A.,de Souza, J.R.T.,Cheleski, J.,DeMarco, R.,Brandao-Neto, J.,Pereira, H.D.
Structure and kinetics assays of recombinant Schistosoma mansoni dihydrofolate reductase.
Acta Trop., 170:190-196, 2017

PubMed Abstract: The parasite Schistosoma mansoni possesses all pathways for pyrimidine biosynthesis, in which dihydrofolate reductase (DHFR), thymidylate cycle participants, is essential for nucleotide metabolism to obtain energy and structural nucleic acids. Thus, DHFRs have been widely suggested as therapeutic targets for the treatment of infectious diseases. In this study, we expressed recombinant SmDHFR in a heterologous manner to obtain structural, biochemical and kinetic information. X-ray diffraction of recombinant SmDHFR at 1.95Å resolution showed that the structure exhibited the canonical DHFR fold. Isothermal titration calorimetry was used to determine the kinetic constants for NADP and dihydrofolate. Moreover, inhibition assays were performed using the commercial folate analogs methotrexate and aminopterin; these analogs are recognized as folate competitors and are used as chemotherapeutic agents in cancer and autoimmune diseases. This study provides information that may prove useful for the future discovery of novel drugs and for understanding these metabolic steps from this pathway of S. mansoni, thus aiding in our understanding of the function of these essential pathways for parasite metabolism.

PubMed: 28288799
DOI: 10.1016/j.actatropica.2017.03.007

Experimental method

X-RAY DIFFRACTION (1.946 Å)