Biochemical and functional properties of a new l-amino acid oxidase (LAAO) from Micrurus lemniscatus snake venom

Int J Biol Macromol. 2020 Jul 1:154:1517-1527. doi: 10.1016/j.ijbiomac.2019.11.033. Epub 2019 Nov 20.

Abstract

This study reports the purification of ML-LAAO, a new LAAO from the venom of Micrurus lemniscatus snake (ML-V), using size exclusion chromatography. ML-LAAO is a 69-kDa glycoprotein that represents ~2.0% of total venom proteins. This enzyme exhibited optimal activity at pH 8.5, displaying high specificity toward hydrophobic l-amino acids. MALDI TOF/TOF and Blast analysis identified internal segments in ML-LAAO that share high sequence identity with homologous snake venom LAAOs. Western blot analysis on two-dimensional SDS-PAGE of ML-V, using anti-LAAO revealed the presence of ML-LAAO isoforms (pI 6.3-8.9). ML-LAAO blocked aggregation induced by collagen on washed platelets in a rather weak manner, it did not, however, inhibit platelet aggregation induced by ADP on platelet-rich plasma. In addition, this enzyme displayed in vitro antibacterial activity against Staphylococcus aureus (MIC/MBC of 0.39 μg/mL) and in vitro leishmanicidal action against Leishmania amazonensis and L. chagasi (IC50 values of 0.14 and 0.039 μg/mL, respectively). These activities were significantly reduced by catalase, suggesting that hydrogen peroxide production is involved in some way. The data presented here revealed that ML-LAAO has bactericidal and leishmanicidal effects, suggesting that it may have therapeutic potential.

Keywords: Micrurus lemniscatus; Snake venom; l-amino acid oxidase.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Coral Snakes*
  • HEK293 Cells
  • Humans
  • L-Amino Acid Oxidase / chemistry*
  • L-Amino Acid Oxidase / pharmacology*
  • Leishmania / drug effects
  • Mice
  • Platelet Aggregation / drug effects
  • RAW 264.7 Cells
  • Snake Venoms / enzymology*

Substances

  • Anti-Bacterial Agents
  • Antiprotozoal Agents
  • Snake Venoms
  • L-Amino Acid Oxidase