General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme
General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme
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DOI：
10.1126/science.287.5457.1493
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发表时间：
2000-02-25
期刊：
影响因子：
56.9
通讯作者：
Bevilacqua, PC
中科院分区：
文献类型：
--
作者：
Nakano, S;Chadalavada, DM;Bevilacqua, PC
许多蛋白质酶使用普通的酸碱催化作为一种提高反应速度的方法。氨基酸组氨酸最适合这一功能，因为它在生理pH附近有一个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断裂。一价阳离子或二价阳离子的反应性-pH曲线，以及到离开基氧的距离，表明核酶的胞嘧啶75(C75)是自切割反应中的总酸，核酶结合的水合金属氢氧化物是总碱。此外，C75有一个PK(A)，它对中性有扰动，使它变得“像组氨酸一样”。观察到质子化的C75与金属离子之间的反协同作用，金属离子对C75的pK(A)起调制作用。一般的酸碱催化扩大了RNA的催化体系，并可能提供更好的速度加速。
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.