Structural highlights
3kjs is a 4 chain structure with sequence from Trycr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 2h2q, 3clb, 3cl9, 3kju, 3kjw |
| Gene: | dhfrts (TRYCR) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[Q8T5T8_TRYCR] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Dihydrofolate reductase (DHFR) of the parasite Trypanosoma cruzi (T. cruzi) is a potential target for developing drugs to treat Chagas' disease. We have undertaken a detailed structure-activity study of this enzyme. We report here synthesis and characterization of six potent inhibitors of the parasitic enzyme. Inhibitory activity of each compound was determined against T. cruzi and human DHFR. One of these compounds, ethyl 4-(5-[(2,4-diamino-6-quinazolinyl)methyl]amino-2-methoxyphenoxy)butanoate (6b) was co-crystallized with the bifunctional dihydrofolate reductase-thymidylate synthase enzyme of T. cruzi and the crystal structure of the ternary enzyme:cofactor:inhibitor complex was determined. Molecular docking was used to analyze the potential interactions of all inhibitors with T. cruzi DHFR and human DHFR. Inhibitory activities of these compounds are discussed in the light of enzyme-ligand interactions. Binding affinities of each inhibitor for the respective enzymes were calculated based on the experimental or docked binding mode. An estimated 60-70% of the total binding energy is contributed by the 2,4-diaminoquinazoline scaffold.
Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase.,Schormann N, Velu SE, Murugesan S, Senkovich O, Walker K, Chenna BC, Shinkre B, Desai A, Chattopadhyay D Bioorg Med Chem. 2010 Jun 1;18(11):4056-66. Epub 2010 Apr 9. PMID:20452776[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schormann N, Velu SE, Murugesan S, Senkovich O, Walker K, Chenna BC, Shinkre B, Desai A, Chattopadhyay D. Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase. Bioorg Med Chem. 2010 Jun 1;18(11):4056-66. Epub 2010 Apr 9. PMID:20452776 doi:10.1016/j.bmc.2010.04.020
