Docking simulation and competitive experiments validate the interaction between the 2, 5-xylidine inhibitor and rigidoporus lignosus laccase

Maria Teresa Cambria, Daniele Di Marino, Mattia Falconi, Silvia Garavaglia, Antonio Cambria

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Laccases are polyphenol oxidases which oxidize a broad range of reducing substrates, preferably phenolic compounds, and their use in biotechnological applications is increasing. Recently, the first X-ray structure of active laccase from white rot fungus Rigidoporus lignosus has been reported containing a full complement of copper ions. Comparison among selected fungal laccases of known 3D structure has shown that the Rigidoporus lignosus laccase has a very high similarity with the Trametes versicolor laccase that, being co-crystallized with 2, 5-xylidine, shows a well defined binding pocket for the substrate. Global sequence alignment between Rigidoporus lignosus and Trametes versicolor laccases shows 73% of identity but, surprisingly, there is no identity and neither conservative substitutions between the residues composing the loops directly contacting the 2, 5-xylidine. Moreover the structural alignment of these two enzymes identifies in these loops a striking structural similarity proposing the question if 2, 5-xylidine may bind in same enzyme pocket. Here we report the protein-ligand docking simulation of 3D structure of Rigidoporus lignosus laccase and 2, 5-xylidine. Docking simulation analyses show that spatial conformation of the two 2, 5-xylidine binding pockets, despite differences in the residues directly contacting the ligand, may arrange a similar pocket that allows a comparable accommodation of the inhibitor. To validate these results the binding of 2, 5-xylidine in the substrate cavity has been confirmed by kinetic competitive experiments.

Lingua originaleInglese
pagine (da-a)501-509
Numero di pagine9
RivistaJournal of Biomolecular Structure and Dynamics
Volume27
Numero di pubblicazione4
DOI
Stato di pubblicazionePubblicato - feb 2010

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