Imidazole ring of His

Crystallographic studies suggest that this is the ionization of the zinc-bound water molecule. The nicotinamide ring of the NAD+ is bound close to the zinc ion at the bottom of the pocket. The 2 -hydroxyl of the ribose ring is located between the hydroxyl of Ser-48 and the imidazole ring of His-51, within hydrogenbonding distance of both. 

The conversion of substrate to product also requires immobilized water molecules within the active site and an appropriate charge environment to facilitate the transfer of electrons and hydrogens to pyruvate. After pyruvate is bound, its reduction to lactate involves addition of two electrons, one proton, and one hydride ion (H ). NADH provides the electrons and hydride ion the proton comes from the imidazole ring of His-193. The rate-determining step in the covalent chemistry taking place in the catalytic vacuole is that of hydride transfer, which occurs at a rate of approximately 750 s 1 at room temperature for bovine A4-LDH (Dunn et al., 1991). 

A remarkable feature of the active site structure in bovine SOD is the presumably deprotonated imidazole ring of His 61 that bridges the two metal ions ... 

The imidazole rings of His 44, His 46, and His 118 are approximately normal to the copper coordination plane, whereas the imidazolate moiety... 

Neutron diffraction studies have shown that the outermost oxygen atom of the boxmd O2 is hydrogen bonded to the H atom on the atom of the distal imidazole ring of His E7 (Fig. 16-10). Carbon monoxide binds with the C=0 axis perpendicular to the heme plane and unable to form a corresponding hydrogen bond. This decreases the affinity for CO and helps to protect us from carbon monoxide poisoning. 

The high basicity of imidazole in comparison with other azoles has been attributed to the stability of the symmetrical imidazolium cation. That pyrazole is less basic can be ascribed to extra destabilization of the 7r-system on protonation <8iJHCl 189). Imidazole s pATj value of close to seven has ramifications for the biological activity of the histidine unit, for example, the two imidazole rings of His 12 and Hisl 19 in Ribonuclease A act as both acid and basic catalysts in the hydrolytic cleavage of RNA <91ACR317>. Some pK. values for substituted imidazoles are tabulated in Table... 

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