Multi-Pole Approach to Structural Science

Warsaw
May 10 - 13, 2015

The structural studies of the two isoforms of laccase from the white-rot fungi Pycnoporus sanguineus
Grzegorz Bujacz

Laccases (EC 1.10.3.2, benzenodiol oxygen oxidoreductases) are enzymes that have the ability to catalyze the oxidation of a wide spectrum of phenolic compounds with the four-electron reduction of molecular oxygen to water [1]. The active site is well conserved among all species. It contains four copper atoms: one paramagnetic type 1 cooper (T1) that is responsible for their characteristic blue color and where the oxidation of the reducing substrate occurs, one type 2 cooper (T2) and two type 3 coopers (T3) that conform a trinuclear cluster in which molecular oxygen is reduced to two molecules of water [2]. Laccases are widely distributed in plants, lichens, bacteria and insects. However, these enzymes are particularly abundant in fungi, having been found in almost all wood-rotting fungi analyzed to date. In most cases laccases are monomeric glycoproteins of around 500 amino acids with molecular weights in the range of 60-85 kDa. The various functions carried out by those enzymes include the antagonistic ones such as their involvement in lignin biosynthesis (in plants), lignin degradation, pigment production, fruiting body formation, pathogenesis (in fungi) and spore protection against UV light (in bacteria) [1, 3]. The diversified functions of laccases make them an interesting enzyme for study from the point of view of their structure, function and application. Laccases of white-rot fungi (WRF) are of special interest because one of their roles is to degrade lignin and most of them are extracellular enzymes helping purification procedures [1]. During the last two decades, there has been an increasing interest in the genus Pycnoporus for its ability to overproduce high redox potential laccases as the ligninolytic enzymes.

We present the crystal structures of two thermostable lacasses produced by strain Pycnoporus sanguineus CS43 (LacI and LacII). The molecular weights of LacI and LacII, determined by SDS-electrophoresis, is 68 and 66 kDa, respectively [3]. Both isoforms show high amino acids sequence similarity (91%) and high thermal stability, at 50°C and 60°C. They remain active at high concentration of organic solvent (acetonitrile, ethanol or acetone). The unique properties make them promising candidates for industrial applications in wastewater treatment. LacI exerted a higher thermal and pH stability, tolerance against inhibitors and was a more efficient catalyst for ABTS and DMP (laccases substrate) than LacII [3]. Based on the structures we would like to understand the isoform differences that cause LacI’s markedly better pH and thermal stability as well as better resistance to inhibitors.

[1] Baldrian F., FEMS Microbiol. Rev., 30, 215–242 (2006)

[2] Mot A. & Silaghi-Dumitrescu R., Biochemistry, 77, 1395-497 (2012)

[3] Rivera-Hoyos E. et al., Fungal Biol. Rev., 27, 67-82 (2013)

[4] Ramirez-Cavazos L. et al., J. Mol. Catal. B Enzym., 108, 32-42 (2014)