Article: Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine
| Title | Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Zhu, AY1 Zhou, Y1 Khan, S1 Deitsch, KW2 Hao, Q1 3 Lin, H1 | ||||||
| Issue Date | 2012 | ||||||
| Publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/acbcct/index.html | ||||||
| Citation | Acs Chemical Biology, 2012, v. 7 n. 1, p. 155-159 [How to Cite?] DOI: http://dx.doi.org/10.1021/cb200230x | ||||||
| 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 sugget 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. © 2011 American Chemical Society. | ||||||
| ISSN | 1554-8929 2011 Impact Factor: 6.446 2011 SCImago Journal Rankings: 0.909 | ||||||
| DOI | http://dx.doi.org/10.1021/cb200230x | ||||||
| ISI Accession Number ID | WOS:000299241300016
Funding Information: This work is supported in part by NIH R01GM086703 (H.L.), NIH RR01646 (Q.H.), and Hong Kong GRF766510 (Q.H.). A.Y.Z. is a CBI training grant trainee (NIH T32 GM08500). | ||||||
| PubMed Central ID | PMC3262940 | ||||||
| References | References in Scopus |
| dc.contributor.author | Zhu, AY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Zhou, Y | ||||||
| dc.contributor.author | Khan, S | ||||||
| dc.contributor.author | Deitsch, KW | ||||||
| dc.contributor.author | Hao, Q | ||||||
| dc.contributor.author | Lin, H | ||||||
| dc.date.accessioned | 2012-02-28T01:55:53Z | ||||||
| dc.date.available | 2012-02-28T01:55:53Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.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 sugget 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. © 2011 American Chemical Society. | ||||||
| dc.description.nature | link_to_OA_fulltext | ||||||
| dc.identifier.citation | Acs Chemical Biology, 2012, v. 7 n. 1, p. 155-159 [How to Cite?] DOI: http://dx.doi.org/10.1021/cb200230x | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1021/cb200230x | ||||||
| dc.identifier.epage | 159 | ||||||
| dc.identifier.hkuros | 198781 | ||||||
| dc.identifier.isi | WOS:000299241300016
Funding Information: This work is supported in part by NIH R01GM086703 (H.L.), NIH RR01646 (Q.H.), and Hong Kong GRF766510 (Q.H.). A.Y.Z. is a CBI training grant trainee (NIH T32 GM08500). | ||||||
| dc.identifier.issn | 1554-8929 2011 Impact Factor: 6.446 2011 SCImago Journal Rankings: 0.909 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.pmcid | PMC3262940 | ||||||
| dc.identifier.pmid | 21992006 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84862907582 | ||||||
| dc.identifier.spage | 155 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/145584 | ||||||
| dc.identifier.volume | 7 | ||||||
| dc.language | eng | ||||||
| dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/acbcct/index.html | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | ACS Chemical Biology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Histones - metabolism | ||||||
| dc.subject.mesh | Lysine - metabolism | ||||||
| dc.subject.mesh | Plasmodium falciparum - enzymology - genetics - immunology | ||||||
| dc.subject.mesh | Protozoan Proteins - chemistry - genetics - metabolism | ||||||
| dc.subject.mesh | Sirtuins - chemistry - genetics - metabolism | ||||||
| dc.title | Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine | ||||||
| dc.type | Article |
Author Affiliations
- Cornell University
- Weill Cornell Medical College
- The University of Hong Kong