Cystathionine gamma- lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp

Autor(es)

Giordana, Lucila ^[1] ; Mantilla, Brian Suarez ^[2] ; Santana, Marianela ^[1] ; Silber, Ariel M. ^[2] ; Nowicki, Cristina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Buenos Aires, Fac Farm & Bioquim, Inst Quim & Fisicoquim Biol IQUIFIB CONICET, Buenos Aires, DF - Argentina

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Eukaryotic Microbiology; v. 61, n. 2, p. 204-213, MAR 2014.
• Citações Web of Science: 8

Resumo

Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine -synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine -lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65M. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug. (AU)

• Processo FAPESP: 11/50631-1 - Metabolismo de histidina: o papel da via histina-glutamato na biologia do Trypanosoma cruzi
• Beneficiário: Ariel Mariano Silber
• Modalidade de apoio: Auxílio à Pesquisa - Regular