title: Sir2-Related Protein 1 from Leishmania amazonensis is a glycosylated NAD+-dependent deacetylase.
abstract: Sirtuin proteins form a family of NAD+-dependent protein deacetylases that are considered potential drug targets against parasites. Here, we present the first characterization of a sirtuin orthologue from Leishmania amazonensis, an aetiological agent of American tegumentary leishmaniasis that has been the subject of many studies focused in the development of therapeutic approaches. The protein has high sequence identity with other Kinetoplastid Silent information regulator 2 Related Protein 1 (Sir2RP1) and was named LaSir2RP1. The gene exists as a single copy, encoding a monomeric protein (LaSir2RP1) of approximately 41 kDa that has NAD+-dependent deacetylase activity. LaSir2RP1 was immunodetected in total protein extracts, in cytoplasmic granules, and in the secreted material of both promastigotes and lesion-derived amastigotes. Analysis of both lectin‑affinity purified promastigote and amastigote extracts revealed the presence of a major enriched protein of approximately 66 kDa that was recognized by an anti-LaSir2RP1 serum, suggesting that a parasite sirtuin could be glycosylated in vivo.
authors.affiliation: Chemistry Institute, University of Campinas UNICAMP, Campinas SP 13083-970, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Fessel
authors.forename: C B
authors.initials: CB
authors.lastname: Lira
authors.forename: S
authors.initials: S
authors.lastname: Giorgio
authors.forename: C H I
authors.initials: CH
authors.lastname: Ramos
authors.forename: M I N
authors.initials: MI
authors.lastname: Cano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000201:enzymology*; D004926:Escherichia coli; D018628:Gene Dosage; D006031:Glycosylation; D006801:Humans; D007120:Immunochemistry; D007894:Leishmania mexicana / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D037761:Sirtuins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D011994:Recombinant Proteins; D009243:NAD; D037761:Sirtuins