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Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine.

TitlePlasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine.
Publication TypeJournal Article
Year of Publication2012
AuthorsZhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H
JournalACS Chem Biol
Volume7
Issue1
Pagination155-9
Date Published2012 Jan 20
ISSN1554-8937
KeywordsAcylation, Amino Acid Sequence, Antigenic Variation, Escherichia coli, Histones, Humans, Hydrolysis, Immune Evasion, Kinetics, Lysine, Models, Molecular, Molecular Sequence Data, Plasmodium falciparum, Protozoan Proteins, Recombinant Proteins, Sirtuins, Substrate Specificity
Abstract

Plasmodium falciparum Sir2A (PfSir2A), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, has been shown to regulate the expression of surface antigens to evade the detection by host immune surveillance. It is thought that PfSir2A achieves this by deacetylating histones. However, the deacetylase activity of PfSir2A is weak. Here we present enzymology and structural evidence supporting that PfSir2A catalyzes the hydrolysis of medium and long chain fatty acyl groups from lysine residues more efficiently. Furthermore, P. falciparum proteins are found to contain such fatty acyl lysine modifications that can be removed by purified PfSir2A in vitro. Together, the data suggest that the physiological function of PfSir2A in antigen variation may be achieved by removing medium and long chain fatty acyl groups from protein lysine residues. The robust activity of PfSir2A would also facilitate the development of PfSir2A inhibitors, which may have therapeutic value in malaria treatment.

DOI10.1021/cb200230x
Alternate JournalACS Chem Biol
PubMed ID21992006
PubMed Central IDPMC3262940
Grant ListR01 GM086703-03 / GM / NIGMS NIH HHS / United States
T32 GM08500 / GM / NIGMS NIH HHS / United States
RR01646 / RR / NCRR NIH HHS / United States
R01GM086703 / GM / NIGMS NIH HHS / United States
T32 GM008500 / GM / NIGMS NIH HHS / United States
P41 RR001646-30 / RR / NCRR NIH HHS / United States
R01 GM086703 / GM / NIGMS NIH HHS / United States
P41 RR001646 / RR / NCRR NIH HHS / United States
T32 GM008500-13 / GM / NIGMS NIH HHS / United States

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