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N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N-Myristoyltransferase Substrates in the Inhibitor Mode of Action.

Abstract：

:Malaria continues to be a significant cause of death and morbidity worldwide, and there is a need for new antimalarial drugs with novel targets. We have focused as a potential target for drug development on N-myristoyl transferase (NMT), an enzyme that acylates a wide range of substrate proteins. The NMT substrates in Plasmodium falciparum include some proteins that are common to processes in eukaryotes such as secretory transport and others that are unique to apicomplexan parasites. Myristoylation facilitates a protein interaction with membranes that may be strengthened by further lipidation, and the inhibition of NMT results in incorrect protein localization and the consequent disruption of function. The diverse roles of NMT substrates mean that NMT inhibition has a pleiotropic and severe impact on parasite development, growth, and multiplication. To study the mode of action underlying NMT inhibition, it is important to consider the function of proteins upstream and downstream of NMT. In this work, we therefore present our current perspective on the different functions of known NMT substrates as well as compare the inhibition of cotranslational myristoylation to the inhibition of known targets upstream of NMT.

journal_name

ACS Infect Dis

journal_title

ACS infectious diseases

authors

Schlott AC,Holder AA,Tate EW

doi

10.1021/acsinfecdis.7b00203

subject

Has Abstract

pub_date

2018-04-13 00:00:00

pages

449-457

issue

4

issn

2373-8227

journal_volume

4

pub_type

杂志文章,评审

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