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The refined 2.4-A structure of adenosine deaminase, recently discovered to be a
zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991)
Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine
shows the mode of binding of the analog and, unexpectedly, a zinc-activated
water (hydroxide). This structure of a pre-transition-state mimic, combined with
that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine
ribonucleoside, a nearly ideal transition-state analog, sheds new understanding
of the precise stereospecificity and hydrolytic catalysis of an important and
well-characterized member of a large group of zinc metalloenzymes. As both of
these excellent mimics were generated in the active site, they demonstrate a
powerful means of dissecting the course of an enzymatic reaction by direct
crystallographic analysis.
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