Structural basis for heterogeneous phenotype of ERG11 dependent Azole resistance in C.albicans clinical isolates.

ABSTRACT: Correlating antifungal Azole drug resistance and mis-sense mutations of ERG11 has been paradoxical in pathogenic yeast Candida albicans. Amino acid substitutions (single or multiple) are frequent on ERG11, a membrane bound enzyme of Ergosterol biosynthesis pathway. Presence or absence of mutations can not sufficiently predict susceptibility. To analyze role of mis-sense mutations on Azole resistance energetically optimized, structurally validated homology model of wild C.albicans ERG11 using eukaryotic template was generated. A Composite Search Approach is proposed to identify vital residues for interaction at 3D active site. Structural analysis of catalytic groove, dynamics of substrate access channels and proximity of Heme prosthetic group characterized ERG11 active site. Several mis-sen

SUBMITTER: Debnath S 

PROVIDER: S-EPMC4237678 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature