Location: Crop Improvement and Genetics ResearchTitle: Structural dynamics of lytic polysaccharide monoxygenases reveals a highly flexible substrate binding region Author
|Arora, R. - Jaypee University Of Information Technology|
|Bharyal, P. - Jaypee University Of Information Technology|
|Sarswati, S. - Jaypee University Of Information Technology|
|Yennamalli, Ragothaman - Jaypee University Of Information Technology|
Submitted to: Journal of Molecular Graphics and Modeling
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/18/2018
Publication Date: 12/29/2018
Citation: Arora, R., Bharyal, P., Sarswati, S., Sen, T.Z., Yennamalli, R.M. 2018. Structural dynamics of lytic polysaccharide monoxygenases reveals a highly flexible substrate binding region. Journal of Molecular Graphics and Modeling. 88(2019)1-10. https://doi.org/10.1016/j.jmgm.2018.12.012.
DOI: https://doi.org/10.1016/j.jmgm.2018.12.012 Interpretive Summary: Cellulose, the most abundant polymer found in plant biomass, presents itself as a unique and promising means to alleviate the current energy needs. Although cellulose, present in plant cell wall, is a recalcitrant polymer, nature has found numerous ways to break it down via cellulases, a broad class of enzymes that degrade cellulose. Lytic polysaccharide monooxygenases have the capability to act on recalcitrant polysaccharides, such as chitin and cellulose. Understanding their enzymatic dynamics and mechanism of action will help researchers develop more efficient enzymes to break down plant biomass to respond to global energy needs.
Technical Abstract: Lytic polysaccharide monooxygenases (LPMOs), which are found in fungi, bacteria, and viruses, are redox enzymes utilizing copper to break glycosidic bonds in recalcitrant crystalline form of polysaccharides, such as chitin and cellulose. They are classified by the Carbohydrate-Active enZYmes (CAZy) database under four families (AA9, AA10, AA11, and AA13). LPMOs’s unusually “rigid” structure with a “flat” active site region has been shown to contribute to its function, however, the role that LPMOs structural dynamics play during polysaccharide degradation and its mechanism of binding towards substrate are relatively unknown. Here, we report an exhaustive implementation of coarse-grained simulations using Elastic Network Models on multiple LPMO structures to shed light on how their structural dynamics contribute to their chemical function. We show that the active site region is highly flexible with significant and sustained micro-scale level conformational changes. Significantly the loops on the binding side of the substrate are most mobile, in concert with the dynamic modes influencing the motions at the active site during binding. We also delineate dynamic differences between the four families that informs on substrate specificity.