Engineering dimer mutants of human geranylgeranyl pyrophosphate synthase.

ABSTRACT: Geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in protein prenylation, plays a critical role in cellular signal transduction and is a promising target for cancer therapy. However, the enzyme's native hexameric quaternary structure presents challenges for crystallographic studies. The primary objective of this study was to engineer dimeric forms of human GGPPS to facilitate high-resolution crystallographic analysis of its ligand binding interactions. Through site-directed mutagenesis, we disrupted the inter-dimer interactions required for hexamer assembly, generating three stable double-site mutants: Y246D/C247L, Y246D/C205A, and Y246K/C247L. Enzyme assays confirmed that all mutants retained wild-type catalytic activity under both saturating and subsaturating substrate conditio

SUBMITTER: Ezekiel SJ 

PROVIDER: S-EPMC11734896 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature