Adenosine Kinase couples sensing of cellular potassium depletion to purine metabolism.

ABSTRACT: Adenosine Kinase (ADK) regulates the cellular levels of adenosine (ADO) by fine-tuning its metabolic clearance. The transfer of γ-phosphate from ATP to ADO by ADK involves regulation by the substrates and products, as well as by Mg²⁺ and inorganic phosphate. Here we present new crystal structures of mouse ADK (mADK) binary (mADK:ADO; 1.2 Å) and ternary (mADK:ADO:ADP; 1.8 Å) complexes. In accordance with the structural demonstration of ADO occupancy of the ATP binding site, kinetic studies confirmed a competitive model of auto-inhibition of ADK by ADO. In the ternary complex, a K⁺ ion is hexacoordinated between loops adjacent to the ATP binding site, where Asp310 connects the K⁺ coordination sphere to the ATP binding site through an anion hole structure. Nuc

SUBMITTER: de Oliveira RR 

PROVIDER: S-EPMC6086891 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature