Fluorescence Spectroscopy Reveals Resveratrol Binding to a Hydrophobic Pocket in Leishmania amazonensis Sir2-Related Protein 1 (LaSir2RP1)

Author(s)

Fessel, Melissa R. ; Povinelli, Ana P. R. ; Fontes, Veronica S. ; Cano, Maria Isabel N. ; Ramos, Carlos H. I.

• Document type: Journal article
• Source: The Protein Journal; v. N/A, p. 12-pg., 2025-06-22.

Abstract

Resveratrol, a natural phytoalexin synthesized by certain plants in response to injury, exhibits antimicrobial properties and various medically significant effects, including anticancer and antiaging activities. Although its exact mechanism of action is still under investigation, it is believed to involve its interaction with a group of protein deacetylases known as sirtuins. Sirtuins are crucial in regulating metabolism, stress responses, and processes such as lifespan extension through caloric restriction. In this study, we report the inhibitory effect of resveratrol on the growth of Leishmania amazonensis promastigotes, highlighting its potential as a microbicide. Through fluorescence spectroscopy assays and in silico analysis, we identified and characterized the interaction between resveratrol and Sir2-related protein 1 from L. amazonensis (rLaSir2RP1). Our results demonstrate a direct interaction between resveratrol and rLaSir2RP1, characterized by a binding constant of 105 M-1. This interaction involves a single binding site located near a hydrophobic pocket, which includes its solely tryptophan residue. (AU)

• FAPESP's process: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/10199-0 - Mapping contact regions between cochaperones from Hsp40 family and proteins involved in amyloidogenic diseases towards the understanding of the mechanisms for protein aggregates reactivation
• Grantee: Ana Paula Ribeiro Povinelli
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/51534-0 - Functional and biophysical studies for LaSir2RP1, sirtuin of Leishmania amazonensis
• Grantee: Melissa Regina Fessel
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/04375-2 - Studies about the biogenesis and composition of the Leishmania spp. ribonucleoprotein complex and its regulation
• Grantee: Maria Isabel Nogueira Cano
• Support Opportunities: Research Projects - Thematic Grants