Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. Academic Article uri icon

Overview

MeSH

  • Acylation
  • Amino Acid Sequence
  • Antigenic Variation
  • Escherichia coli
  • Humans
  • Hydrolysis
  • Immune Evasion
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Recombinant Proteins
  • Substrate Specificity

MeSH Major

  • Histones
  • Lysine
  • Plasmodium falciparum
  • Protozoan Proteins
  • Sirtuins

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.

publication date

  • January 20, 2012

has subject area

  • Acylation
  • 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

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3262940

Digital Object Identifier (DOI)

  • 10.1021/cb200230x

PubMed ID

  • 21992006

Additional Document Info

start page

  • 155

end page

  • 159

volume

  • 7

number

  • 1