Crystal structure and molecular dynamics studies of L-amino acid oxidase from Bothrops atrox

Author(s)

Feliciano, Patricia R. ; Rustiguel, Joane K. ; Soares, Ricardo O. S. ; Sampaio, Suely V. ; Cristina Nonato, M.

• Document type: Journal article
• Source: Toxicon; v. 128, p. 50-59, MAR 15 2017.
• Web of Science Citations: 8

Abstract

L-amino acid oxidases (LAAOs) are dimeric flavoproteins that catalyze the deamination of L-amino acid to alpha-keto acid, producing ammonia and hydrogen peroxide. In this study, we report the crystal structure and molecular dynamics simulations of LAAO from the venom of Bothrops atrox (BatroxLAAO). BatroxLAAO presents several biological and pharmacological properties with promising biomedical applications. BatroxLAAO structure contains the highly conserved structural pattern of LAAOs comprising a FAD binding domain, substrate-binding domain and helical domain, and a dimeric arrangement that can be stabilized by zinc. Also, molecular dynamics results show an asymmetric behavior, and a direct communication between FAD- and substrate-binding domains of counterpart subunits. These findings shed light on the structural role of dimerization to catalytic mechanism of SV-LAAOs. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 15/24010-0 - Structural and biophysical characterization of animal toxins
• Grantee: Joane Kathelen Rustiguel Bonalumi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/10454-3 - Studies of the correlation between structure and function of the enzyme fumarate hydratase in Leishmania major
• Grantee: Patrícia Rosa Feliciano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/14988-8 - Elucidation of the mechanism of action of fumarate hydratase from Leishmania major
• Grantee: Patrícia Rosa Feliciano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral