New insights into the molecular characteristics behind the function of Renilla luciferase

J Cell Biochem. 2018 Feb;119(2):1780-1790. doi: 10.1002/jcb.26339. Epub 2017 Nov 16.

Abstract

Renilla Luciferase (RLuc) is a blue light emitter protein which can be applied as a valuable tool in medical diagnosis. But due to lack of the crystal structure of RLuc-ligand complex, the functional motions and catalytic mechanism of this enzyme remain largely unknown. In the present study, the active site properties and the ligand-receptor interactions of the native RLuc and its red-shifted light emitting variant (Super RLuc 8) were investigated using molecular docking approach, molecular dynamics (MD) analysis, and MM-PBSA method. The detailed analysis of the main clusters led to identifying a lid-like structure and its functional motions. Furthermore, an induced-fit mechanism is proposed where ligand-binding induces conformational changes of the active site. Our findings give an insight into the deeper understanding of RLuc conformational changes during binding steps and ligand-receptor pattern. Moreover, our work broaden our understanding of how active site geometry is adjusted to support the catalytic activity and red-shifted light emission in Super RLuc 8.

Keywords: MM-PBSA method; Renilla luciferase (RLuc); molecular docking; molecular dynamic (MD) simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Ligands
  • Luciferases, Renilla / chemistry*
  • Luciferases, Renilla / genetics
  • Luciferases, Renilla / metabolism*
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Mutagenesis, Site-Directed*
  • Protein Binding
  • Protein Conformation

Substances

  • Ligands
  • Luciferases, Renilla