2WV2

X-ray structure of CYP51 from the human pathogen Trypanosoma brucei in complex with fluconazole

2WV2 の概要

• エントリーDOI: 10.2210/pdb2wv2/pdb
• 関連するPDBエントリー: 2WUZ 2WX2
• 分子名称: LANOSTEROL 14-ALPHA-DEMETHYLASE, 2-(2,4-DIFLUOROPHENYL)-1,3-DI(1H-1,2,4-TRIAZOL-1-YL)PROPAN-2-OL, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, methyltransferase, p450, iron, cyp51, metal-binding, ergosterol biosynthesis
• 由来する生物種: TRYPANOSOMA BRUCEI
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54898.35

構造登録者

Chen, C.-K.,Leung, S.S.F.,Guilbert, C.,Jacobson, M.,McKerrow, J.H.,Podust, L.M. (登録日: 2009-10-12, 公開日: 2009-11-10, 最終更新日: 2024-05-08)

主引用文献

Chen, C.-K.,Leung, S.S.F.,Guilbert, C.,Jacobson, M.,Mckerrow, J.H.,Podust, L.M.
Structural Characterization of Cyp51 from Trypanosoma Cruzi and Trypanosoma Brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole
Plos Negl Trop Dis, 4:E651-, 2010

PubMed Abstract: Chagas Disease is the leading cause of heart failure in Latin America. Current drug therapy is limited by issues of both efficacy and severe side effects. Trypansoma cruzi, the protozoan agent of Chagas Disease, is closely related to two other major global pathogens, Leishmania spp., responsible for leishmaniasis, and Trypansoma brucei, the causative agent of African Sleeping Sickness. Both T. cruzi and Leishmania parasites have an essential requirement for ergosterol, and are thus vulnerable to inhibitors of sterol 14alpha-demethylase (CYP51), which catalyzes the conversion of lanosterol to ergosterol. Clinically employed anti-fungal azoles inhibit ergosterol biosynthesis in fungi, and specific azoles are also effective against both Trypanosoma and Leishmania parasites. However, modification of azoles to enhance efficacy and circumvent potential drug resistance has been problematic for both parasitic and fungal infections due to the lack of structural insights into drug binding.

PubMed: 20386598
DOI: 10.1371/JOURNAL.PNTD.0000651

実験手法

X-RAY DIFFRACTION (2.7 Å)