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3u3d
From Proteopedia
Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine
Structural highlights
Function[SIR5_PLAF7] NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedPlasmodium 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. Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine.,Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H ACS Chem Biol. 2011 Oct 21. PMID:21992006[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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