Journal article
Probing function & structure of trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct molecular groupings
M Cross, R Lepage, S Rajan, S Biberacher, ND Young, BN Kim, MJ Coster, RB Gasser, JS Kim, A Hofmann
FASEB Journal | Published : 2017
Abstract
The trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccharide in many pathogens but is neither required nor synthesized in mammalian hosts. As such, trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis, is likely an attractive target for novelchemotherapeutics.Basedona survey ofgenomes froma panel of parasiticnematodes and bacterial organisms and by way of a structure-based amino acid sequence alignment, we derive the topological structure of monoenzyme TPPs and classify them into 3 groups. Comparison of the functional roles of amino acid residues located in the active site for TPPs ..
View full abstractGrants
Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by grants from the Australian Research Council, the National Health and Medical Research Council (NHMRC) (to A.H., R.B.G., and N.D.Y.), the Rebecca L.Cooper Medical Research Foundation (to A.H.), and Chonnam National University (Grant 2015-0597 to J.- S.K.); by an Equity Trustees PhD Scholarship ( to M. C.); and by the NHMRC Career Development Fellowship (to N. D. Y.). The authors thank Robert Huber (Max Planck Institute of Biochemistry, Martinsried, Germany) for fruitful discussions during this study and James Cameron (Griffith University) for help with the inductively coupled plasma atomic emission spectroscopy measurements. Mass spectrometric analysis was undertaken at the Australian Proteome Analysis Facility provided by the Australian Government through the National Collaborative Research Infrastructure Strategy.