3U3D

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

Summary for 3U3D

• Entry DOI: 10.2210/pdb3u3d/pdb
• Related: 3U31
• Descriptor: Transcriptional regulatory protein sir2 homologue, histone 3 myristoyl lysine 9 peptide, GLYCEROL, ... (5 entities in total)
• Functional Keywords: zn-binding domain, rossmann fold domain, nad-dependent deacylase, hydrolase
• Biological source: Plasmodium falciparum; More
• Cellular location: Nucleus, nucleolus: Q8IE47
• Total number of polymer chains: 2
• Total formula weight: 33825.66

Authors

Zhou, Y.,Hao, Q. (deposition date: 2011-10-05, release date: 2011-11-09, Last modification date: 2023-11-01)

Primary citation

Zhu, A.Y.,Zhou, Y.,Khan, S.,Deitsch, K.W.,Hao, Q.,Lin, H.
Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine
Acs Chem.Biol., 2011

PubMed 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.

PubMed: 21992006
DOI: 10.1021/cb200230x

Experimental method

X-RAY DIFFRACTION (2.4 Å)