Crystallographic Structure and Antiglioma Potential ofSeed Lectin.

in ACS omega by Benildo Sousa Cavada, Vanir Reis Pinto-Junior, Francisco Edilcarlos Oliveira Lima, Valeria Maria Sousa Ferreira, Messias Vital Oliveira, Vinicius Jose Silva Osterne, Nicole Sartori, Ana Carolina Dos Santos, Rodrigo Bainy Leal, Kyria Santiago Nascimento

TLDR

  • The study characterizes the structure and carbohydrate-binding properties of a mannose-specific lectin from the Dalbergieae tribe and evaluates its potential against gliomas, highlighting its structural characteristics and functional limitations.

Abstract

The genuscomprises species of Neotropical trees with seeds that possess medicinal and bioactive applications. Lectins from this genus exhibit anti-inflammatory and immunomodulatory effects, influencing the activation of the immune system. This study focuses on characterizing the structure and carbohydrate-binding properties of the lectin from(CML) and evaluating its potential against gliomas. The structure of the lectin in complex with methyl-mannose-α1,3-mannose (MDM) was resolved using X-ray crystallography at 1.3 Å resolution, with its interactions further analyzed through molecular dynamics simulations. Structurally, CML adopts a β-sandwich motif and assembles into canonical dimers.assays revealed that CML reduced the viability of C6 glioma cells, although only at high concentrations, without impacting cell migration or morphology. CML activated autophagic processes, albeit with lower efficacy compared with other mannose-specific lectins. The limited antiglioma activity of CML may be linked to its inability to form tetramers and unusual specificity toward asymmetric glycans, both crucial features for interactions with cellular glycans and the activation of signaling pathways. This study represents the first investigation of the antiglioma potential of a mannose-specific lectin from the Dalbergieae tribe, highlighting both its structural characteristics and functional limitations.

Overview

  • The study focuses on characterizing the structure and carbohydrate-binding properties of the lectin from (CML) and evaluating its potential against gliomas.
  • The lectin from CML exhibits anti-inflammatory and immunomodulatory effects influencing the activation of the immune system.
  • The primary objective of the study is to investigate the antiglioma potential of a mannose-specific lectin from the Dalbergieae tribe.

Comparative Analysis & Findings

  • The study revealed that CML adopts a β-sandwich motif and assembles into canonical dimers.
  • CML reduced the viability of C6 glioma cells, although only at high concentrations, without impacting cell migration or morphology.
  • CML activated autophagic processes, but with lower efficacy compared with other mannose-specific lectins.

Implications and Future Directions

  • The study highlights the structural characteristics and functional limitations of CML, indicating its potential for further research and development.
  • Further studies could focus on modifying CML's structure and specificity to enhance its antiglioma activity.
  • The investigation of other mannose-specific lectins from the Dalbergieae tribe could provide valuable insights into their potential therapeutic applications.