title: Modeling and interactions of Aspergillus fumigatus lanosterol 14-alpha demethylase 'A' with azole antifungals.
abstract: Recent identification of the sterol 14-alpha demethylase genes (CYP51 A and B) from Aspergillus fumigatus and other species by Mellado et al. (J. Clin. Microbiol. 2001, 39(7), 2431-2438), has opened up possibilities of investigating the interactions of azole antifungals with the enzyme(s) from fungi. This study describes for the first time, a model of the three-dimensional structure of A. fumigatus 14-alpha demethylase (AF-CYP51A), using the crystal structure of Mycobacterium tuberculosis 14-alpha demethylase (PDB code:1EA1) as a template. The paper also describes the various interactions between azole antifungals and the target from A. fumigatus (AF-CYP51A). Quantitative evaluation of these interactions is done using COMBINE analysis to understand contributions of active site residues to ligand activity. It also provides explanation for the activity/inactivity of different ligands for AF-CYP51A.
authors.affiliation: VLife Science Technologies Pvt. Ltd, 1 Akshay Residency, Plot # 50 Anand Park, Aundh Pune 411 007, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Gollapudy
authors.forename: Subhash
authors.initials: S
authors.lastname: Ajmani
authors.forename: Sudhir A
authors.initials: SA
authors.lastname: Kulkarni
mesh_terms: D020816:Amino Acid Motifs; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000201:enzymology*; D001393:Azoles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D019295:Computational Biology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D008024:Ligands; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus