Nakano S, Chadalavada D M, Bevilacqua P C
Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Science. 2000 Feb 25;287(5457):1493-7. doi: 10.1126/science.287.5457.1493.
Many protein enzymes use general acid-base catalysis as a way to increase reaction rates. The amino acid histidine is optimized for this function because it has a pK(a) (where K(a) is the acid dissociation constant) near physiological pH. The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond. Reactivity-pH profiles in monovalent or divalent cations, as well as distance to the leaving-group oxygen, implicate cytosine 75 (C75) of the ribozyme as the general acid and ribozyme-bound hydrated metal hydroxide as the general base in the self-cleavage reaction. Moreover, C75 has a pK(a) perturbed to neutrality, making it "histidine-like." Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the pK(a) of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.
许多蛋白质酶利用广义酸碱催化来提高反应速率。氨基酸组氨酸针对此功能进行了优化，因为它在生理pH值附近具有一个pK(a)（其中K(a)是酸解离常数）。丁型肝炎病毒的RNA酶（核酶）催化磷酸二酯键的自我切割。在一价或二价阳离子中的反应活性-pH曲线，以及与离去基团氧的距离，表明核酶的胞嘧啶75（C75）在自我切割反应中作为广义酸，而与核酶结合的水合金属氢氧化物作为广义碱。此外，C75的pK(a)被扰动至中性，使其“类组氨酸”。在质子化的C75和金属离子之间观察到反协同相互作用，这有助于调节C75的pK(a)。广义酸碱催化扩展了RNA的催化功能，并且可能提供更好的速率加速。
