A Structural and Bioinformatics Investigation of a Fungal Squalene Synthase and Comparisons with Other Membrane Proteins.

ABSTRACT: There is interest in the development of drugs to treat fungal infections due to the increasing threat of drug resistance, and here, we report the first crystallographic structure of the catalytic domain of a fungal squalene synthase (SQS), Aspergillus flavus SQS (AfSQS), a potential drug target, together with a bioinformatics study of fungal, human, and protozoal SQSs. Our X-ray results show strong structural similarities between the catalytic domains in these proteins, but, remarkably, using bioinformatics, we find that there is also a large, highly polar helix in the fungal proteins that connects the catalytic and membrane-anchoring transmembrane domains. This polar helix is absent in squalene synthases from all other lifeforms. We show that the transmembrane domain in AfSQS and i

SUBMITTER: Malwal SR 

PROVIDER: S-EPMC9260892 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature