In this section
The publication feed below is often incomplete and out of date; for an up to date summary of our publications please see Google Scholar or Pub Med
@article{Wright:2016:10.1021/acsinfecdis.6b00034,
author = {Wright, MH and Paape, D and Price, HP and Smith, DF and Tate, EW},
doi = {10.1021/acsinfecdis.6b00034},
journal = {ACS Infectious Diseases},
pages = {427--441},
title = {Global profiling and inhibition of protein lipidation in vector andhost stages of the sleeping sickness parasite Trypanosoma brucei},
url = {http://dx.doi.org/10.1021/acsinfecdis.6b00034},
volume = {2},
year = {2016}
}
TY - JOUR
AB - The enzyme N-myristoyltransferase (NMT) catalyses the essential fatty acylation ofsubstrate proteins with myristic acid in eukaryotes and is a validated drug target in theparasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleepingsickness). N-Myristoylation typically mediates membrane localisation of proteins and isessential to the function of many. However, only a handful of proteins are experimentallyvalidated as N-myristoylated in T. brucei. Here, we perform metabolic labelling with analkyne-tagged myristic acid analogue, enabling the capture of lipidated proteins in insect and host life stages of T. brucei. We further compare this with a longer chain palmitate analogueto explore the chain length-specific incorporation of fatty acids into proteins. Finally, wecombine the alkynyl-myristate analogue with NMT inhibitors and quantitative chemicalproteomics to globally define N-myristoylated proteins in the clinically relevant bloodstreamform parasites. This analysis reveals five ARF family small GTPases, calpain-like proteins,phosphatases and many uncharacterized proteins as substrates of NMT in the parasite,providing a global view of the scope of this important protein modification and furtherevidence for the crucial and pleiotropic role of NMT in the cell.
AU - Wright,MH
AU - Paape,D
AU - Price,HP
AU - Smith,DF
AU - Tate,EW
DO - 10.1021/acsinfecdis.6b00034
EP - 441
PY - 2016///
SN - 2373-8227
SP - 427
TI - Global profiling and inhibition of protein lipidation in vector andhost stages of the sleeping sickness parasite Trypanosoma brucei
T2 - ACS Infectious Diseases
UR - http://dx.doi.org/10.1021/acsinfecdis.6b00034
UR - http://hdl.handle.net/10044/1/31942
VL - 2
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821