Importance of hydrophobic cavities in allosteric regulation of formylglycinamide synthetase: insight from xenon trapping and statistical coupling analysis.

ABSTRACT: Formylglycinamide ribonucleotide amidotransferase (FGAR-AT) is a 140 kDa bi-functional enzyme involved in a coupled reaction, where the glutaminase active site produces ammonia that is subsequently utilized to convert FGAR to its corresponding amidine in an ATP assisted fashion. The structure of FGAR-AT has been previously determined in an inactive state and the mechanism of activation remains largely unknown. In the current study, hydrophobic cavities were used as markers to identify regions involved in domain movements that facilitate catalytic coupling and subsequent activation of the enzyme. Three internal hydrophobic cavities were located by xenon trapping experiments on FGAR-AT crystals and further, these cavities were perturbed via site-directed mutagenesis. Biophysical characteriza

SUBMITTER: Tanwar AS 

PROVIDER: S-EPMC3815217 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature