Structural Modeling of NTPDase-Substrate Complexes Preserving Catalytic Experimental Features.

ABSTRACT: Members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family play a pivotal role in hydrolyzing nucleoside triphosphates and diphosphates, modulating purinergic and pyrimidinergic signaling pathways. The NTPDases have therapeutic potential; gaining structural insights into NTPDase-substrate complexes would be valuable for optimizing these enzymes for therapeutic applications. However, such insights remain limited, posing challenges for effective optimization. Molecular docking often fails to capture experimentally characterized substrate conformations, leading to biologically irrelevant models. To address this, we developed a computational strategy that preserves experimentally observed substrate features while leveraging the active site's conservation across NTPDases.

SUBMITTER: de Moraes JVB 

PROVIDER: S-EPMC12489842 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature