Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations

摘要: The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. is folded as an eight-stranded parallel alpha/beta barrel deep pocket the beta-barrel COOH-terminal end wherein inhibitor zinc are bound completely sequestered. presence cofactor precise analog were not previously known. 6R isomer very tightly held in place by coordination 6-hydroxyl to formation nine hydrogen bonds. On basis complex stereoselective addition-elimination or SN2 mechanism enzyme proposed atom Glu Asp residues playing key roles. A molecular explanation hereditary disease caused several point mutations also presented.