Structural Dynamics of Lytic PolysaccHaride Monooxygenase

Abstract

Lytic Polysaccharide Monooxygenases (LPMOs) found in fungi, bacteria, and viruses are redox enzymes that utilize copper to cleave glycosidic bonds in the recalcitrant crystalline form of polysaccharides. Cellulose and chitin are currently classified by CAZy under AA9, AA10, AA11, and AA13 families. LPMO’s unusually “flat” and “rigid” active site framework for its catalytic activity has been the focus since their discovery in the early 2000s. LPMOs’ molecular architecture to bind to cellulose and chitin (and other polymers) is most likely evolved due to the presence of a diverse substrate landscape. Here, using structural bioinformatics approach coupled with Elastic Network Modeling (ENM), we compare and contrast the structurally similar yet sequentially and functionally diverse polysaccharide monooxygenases. The structural dynamics studies of AA9, AA10, AA11, and AA13 families indicate that the “rigid” active site is highly flexible than previously hypothesized. Also, the loops on the substrate binding side are most mobile indicating their role in substrate binding. However, there are crucial dynamical and physicochemical differences between the four families that are responsible for their substrate specificity. The study also predicts key residues that are possibly responsible for substrate specificity and LPMO’s function, in other words towards its allostery.