Polysaccharide lyases (PLs) are an important class of proteins that are excreted from bacteria to degrade sugars in the extracellular matrix of the host. The PL from S. maltophilia (Smlt1473) was found to have pH-specific degradation of three varying polysaccharides: alginate, celluronic acid, and hyaluronic acid (J. Biol. Chem. 2014, 289, 18022-18032). In this work, we aim to further understand the effect of pH on sugar binding and cleavage using molecular dynamics (MD) simulations and activity assay experiments. The structure of Smlt1437 was modeled with crystal structure of alginate lyase A1-III (PDB 1QAZ) from Sphingomonas Sp. Ionizable resides were adjusted based on their predicted pK(a)'s at pH of 5, 7, and 9 and simulated in solution with predicted docked structures of hyaluronic acid (HA) and poly-beta-D-glucuronic acid (poly-GlcUA). These docked structures were simulated for 125 ns using all-atom MD. The simulations with monomers of HA and poly-GlcUA revealed the importance of loop1 of the protein to cover the binding pocket. Glu212 was found to be important with cross-domain interactions of loop1 to stabilize a closed binding pocket state. Mutations of this residue (E212G) resulted in significant reduction of enzyme activity compared to the wildtype, which our simulations predict prevents the formation of a stable salt bridge with Arg215. Asp48 on loop1 appears to limit the activity of this enzyme as the D48G mutant shows an increased activity, which based on our MD simulations suggest that Asp48 interactions can block sugar binding with Arg218. MD simulations of the HA 4mer resulted in consistent protein interactions that stabilize sugar binding to Smlt1473 and provide insight into the importance of Trp171 to binding. Overall, this joint experimental/computational study has probed allosteric effects of sugar binding to loop1 stability that influences enzyme activity.