Binding asymmetry and conformational studies of the AtGSDA dimer

Guanosine deaminase (GSDA) is an important deaminase that converts guanosine to xanthosine, a key intermediate in nitrogen recycling in plants. We previously solved complex structures of Arabidopsis thaliana GSDA bound by various ligands and examined its catalytic mechanism. Here, we report cocrystal structures of AtGSDA bound by inactive guanosine derivatives, which bind relatively weakly to the enzyme and mostly have poor binding geometries. The two protomers display unequal binding performances, and molecular dynamics simulation identified diverse conformations during the enzyme-ligand interactions. Moreover, intersubunit, tripartite salt bridges show conformational differences between the two protomers, possibly acting as gating systems for substrate binding and product release. Our structural and biochemical studies provide a comprehensive un-derstanding of the enzymatic behavior of this intriguing enzyme.

Automated summary

This study investigates the structure and function of guanosine deaminase (GSDA). By analyzing the cocrystal structures of Arabidopsis thaliana GSDA bound by inactive guanosine derivatives, it is found that the binding performances of the two protomers are unequal, and molecular dynamics simulation confirms diverse conformations during the enzyme-ligand interactions. Furthermore, tripartite salt bridges between subunits are identified to play a role as gating systems for substrate binding and product release.