 |
PDBsum entry 2wsa
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
N-Myristoyltransferase inhibitors as new leads to treat sleeping sickness.
|
|
|
Authors
|
|
J.A.Frearson,
S.Brand,
S.P.Mcelroy,
L.A.Cleghorn,
O.Smid,
L.Stojanovski,
H.P.Price,
M.L.Guther,
L.S.Torrie,
D.A.Robinson,
I.Hallyburton,
C.P.Mpamhanga,
J.A.Brannigan,
A.J.Wilkinson,
M.Hodgkinson,
R.Hui,
W.Qiu,
O.G.Raimi,
D.M.Van aalten,
R.Brenk,
I.H.Gilbert,
K.D.Read,
A.H.Fairlamb,
M.A.Ferguson,
D.F.Smith,
P.G.Wyatt.
|
|
|
Ref.
|
|
Nature, 2010,
464,
728-732.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
African sleeping sickness or human African trypanosomiasis, caused by
Trypanosoma brucei spp., is responsible for approximately 30,000 deaths each
year. Available treatments for this disease are poor, with unacceptable efficacy
and safety profiles, particularly in the late stage of the disease when the
parasite has infected the central nervous system. Here we report the validation
of a molecular target and the discovery of associated lead compounds with the
potential to address this lack of suitable treatments. Inhibition of this
target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes
both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity
inhibitors bind into the peptide substrate pocket of the enzyme and inhibit
protein N-myristoylation in trypanosomes. The compounds identified have
promising pharmaceutical properties and represent an opportunity to develop oral
drugs to treat this devastating disease. Our studies validate T. brucei
N-myristoyltransferase as a promising therapeutic target for human African
trypanosomiasis.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Myristoyl-Coa:protein n-Myristoyltransferase, An essential enzyme and potential drug target in kinetoplastid parasites.
|
|
|
Authors
|
|
H.P.Price,
M.R.Menon,
C.Panethymitaki,
D.Goulding,
P.G.Mckean,
D.F.Smith.
|
|
|
Ref.
|
|
J Biol Chem, 2003,
278,
7206-7214.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
