4H98
Candida glabrata dihydrofolate reductase complexed with NADPH and 5-{3-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methoxyphenyl]prop-1-yn-1-yl}-6-ethylpyrimidine-2,4-diamine (UCP1018)
Summary for 4H98
| Entry DOI | 10.2210/pdb4h98/pdb |
| Related | 3QLX 3QLY 3QLZ 3RO9 3ROA |
| Descriptor | Dihydrofolate Reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 5-{3-[3-(1,3-benzodioxol-5-yl)-5-methoxyphenyl]prop-1-yn-1-yl}-6-ethylpyrimidine-2,4-diamine, ... (4 entities in total) |
| Functional Keywords | antifungal agents, candida glabrata, drug design, enzyme inhibitors, fungal proteins, tetrahydrofolate dehydrogenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Candida glabrata (yeast) |
| Total number of polymer chains | 2 |
| Total formula weight | 54455.50 |
| Authors | Paulsen, J.L.,Anderson, A.C. (deposition date: 2012-09-24, release date: 2013-03-27, Last modification date: 2023-09-20) |
| Primary citation | Paulsen, J.L.,Viswanathan, K.,Wright, D.L.,Anderson, A.C. Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species. Bioorg.Med.Chem.Lett., 23:1279-1284, 2013 Cited by PubMed Abstract: A novel strategy for targeting the pathogenic organisms Candida albicans and Candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. Crystal structure analysis suggested that an essential loop at the active site (Thr 58-Phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. In order to probe the role of this loop, we employed chemical synthesis, crystal structure determination and molecular dynamics simulations. The results of these analyses show that the loop residues undergo ligand-induced conformational changes that are similar among the fungal and human species. PubMed: 23375226DOI: 10.1016/j.bmcl.2013.01.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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