CRYSTAL-STRUCTURE OF TRICHOSANTHIN-NADPH COMPLEX AT 1.7 ANGSTROM RESOLUTION REVEALS ACTIVE-SITE ARCHITECTURE

We describe here the crystal structure of the trichosanthin-NADPH complex determined at a resolution of 1.7 Angstrom. The adenine base stacks between Tyr 70 and Tyr 111. Aug 163, Glu 160 and Tyr 70 form hydrogen bonds to N(3), O(3') and, through a water molecule, to N(9) of adenosine, respectively. This is the first high resolution structure of a complex between a ribosome-inactivating protein and a substrate analogue, in which the electron density of the IV-glycosidic bond is well defined and the preassociated water, thought to be responsible for hydrolyzing the N-C bond, is also explicitly elucidated.