2X2N

X-ray structure of cyp51 from trypanosoma brucei in complex with posaconazole in two different conformations

Summary for 2X2N

• Entry DOI: 10.2210/pdb2x2n/pdb
• Related: 2WUZ 2WV2 2WX2
• Descriptor: LANOSTEROL 14-ALPHA-DEMETHYLASE, PROTOPORPHYRIN IX CONTAINING FE, POSACONAZOLE, ... (4 entities in total)
• Functional Keywords: oxidoreductase, p450, metal-binding, methyltransferase, ergosterol biosynthesis
• Biological source: TRYPANOSOMA BRUCEI
• Total number of polymer chains: 4
• Total formula weight: 220475.02

Authors

Chen, C.-K.,Leung, S.S.F.,Guilbert, C.,Jacobson, M.,McKerrow, J.H.,Podust, L.M. (deposition date: 2010-01-14, release date: 2010-02-02, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)