Structural glycobiology of heparinase II from Pedobacter heparinus

The current work presents a conformational evaluation of heparinase II (hepII) from Pedobacter heparinus, employing molecular dynamics (MD) simulations, in order to characterize the main features of the enzyme dynamics, as well as the role of the glycan and metal components on the protein scaffold. Accordingly, four systems were simulated, encompassing nonglycosylated hepII without structural ions, nonglycosylated hepII with Zn(2+), nonglycosylated hepII with Ca(2+), and glycosylated hepII with Zn(2+). The obtained data suggest a role for Zn(2+) in modulating the protein flexibility at specific loop regions. Such flexibility pattern is not properly maintained in the absence of such structural ion or when the ion is replaced by Ca(2+). Still, semiempirical calculations suggest more favorable interactions with Zn(2+). These events correlate with the experimentally reported inhibitory effect of calcium over hepII. Additionally, the glycan chain seems able to promote an additional stabilization on hepII dynamics. Taken together, these results improve our understanding of the structural and dynamical features of hepII, as well as atomic-level comprehension of previous experimental data.