title: Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine.
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.
authors: Anita Y
authors: AY
authors: Zhu
authors: Yeyun
authors: Y
authors: Zhou
authors: Saba
authors: S
authors: Khan
authors: Kirk W
authors: KW
authors: Deitsch
authors: Quan
authors: Q
authors: Hao
authors: Hening
authors: H
authors: Lin
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D000940:Antigenic Variation / Q000276:immunology; D004926:Escherichia coli; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D057131:Immune Evasion; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D006657:Histones; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D037761:Sirtuins; D008239:Lysine