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)

4H98 の概要

• エントリーDOI: 10.2210/pdb4h98/pdb
• 関連するPDBエントリー: 3QLX 3QLY 3QLZ 3RO9 3ROA
• 分子名称: 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)
• 機能のキーワード: antifungal agents, candida glabrata, drug design, enzyme inhibitors, fungal proteins, tetrahydrofolate dehydrogenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Candida glabrata (yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54455.50

構造登録者

Paulsen, J.L.,Anderson, A.C. (登録日: 2012-09-24, 公開日: 2013-03-27, 最終更新日: 2023-09-20)

主引用文献

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

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: 23375226
DOI: 10.1016/j.bmcl.2013.01.008

実験手法

X-RAY DIFFRACTION (2.9 Å)