= Solution
\b[His238 contributes strongly to turnover, with a plausible acid/base or electrostatic role near the attacking <water>.] Replacing its <imidazole> by the methyl side chain of <alanine> removes both proton-transfer capacity and a positioned polar group, so the large fall in <turnover number> fits impaired chemical catalysis. A candidate role is acceptance of a proton from zinc-bound <water>, or stabilization and subsequent proton shuttling around the attacking <oxygen>.
Little change in the <Michaelis constant> suggests that the major kinetic defect is not a gross loss of <substrate> recognition, but $K_M$ is not generally a binding <dissociation constant>: $K_M=(k_{-1}+k_{\mathrm{cat}})/k_1$ for the elementary scheme. Nor does reduced $k_{\mathrm{cat}}$ uniquely prove that His238 is the initial general base. Purified-protein controls should check fold, zinc occupancy and active concentration. Importantly, primary mouse-<enzyme> experiments found that His238 mutants could still hydrate a <substrate> analogue, directly illustrating this mechanistic limitation.<Site-directed mutagenesis of histidine 238 in mouse adenosine deaminase: substitution of histidine 238 does not impede hydroxylate formation by V. Sideraki and others>[1996, abstract and pp. 15019–15028, purine-riboside hydration by mutant enzyme]{ref}
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