Role of Graphene Oxide in Inhibiting the Interactions between Nucleoside Diphosphate Kinases -B and -C

Abstract

Nucleoside diphosphate kinase (NDPK) enzyme in the sarcolemma membrane is crucial for the synthesis of cyclic adenosine monophosphate (cAMP) to maintain the calcium ion balance. Typically, NDPK-B residue His118, in the presence of NPDK-C, phosphorylates the stimulatory guanosine diphosphate, GDP(s). During a heart failure, an increased quantity of NDPK-B also phosphorylates the inhibitory GDP(i), thereby inhibiting the cAMP synthesis. In this work, the interactions between NDPK-B and NDPK-C are quantified in the presence and absence of graphene oxide (GO) using molecular dynamics through stability analysis involving hydrogen bonds, center of mass (COM), RMSD, salt bridges, non-bonding energy analysis and interfacial water molecules. It is found that the adsorption of NDPK-B on GO triggers a conformational change in NDPK-B and its reduced interactions with NDPK-C, confirmed through a reduced COM distance between NDPK-B and GO (from 40 Å to 30 Å) and an increased COM distance between NDPK-B and NDPK-C (from 50 Å to 60 Å). This is also supported by fewer salt bridges between NDPK-B and NDPK-C, and an increased number of hydrogen bonds of the interfacial water molecules between NDPK-B and GO. This finding suggests that GO can suppress the interactions among NDPK-B/C complex required for phosphorylation of GDP(i).