Comparison of the Structures and Mechanisms of the Pistol and Hammerhead Ribozymes

被引:44
作者
Wilson, Timothy J. [1 ]
Liu, Yijin [1 ,3 ]
Li, Nan-Sheng [2 ]
Dai, Qing [2 ]
Piccirilli, Joseph A. [2 ]
Lilley, David M. J. [1 ]
机构
[1] Univ Dundee, Canc Res UK Nucle Acid Struct Res Grp, MSI WTB Complex,Dow St, Dundee DD1 5EH, Scotland
[2] Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA
[3] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Haihe Educ Pk,38 Tongyan Rd, Tianjin 300353, Peoples R China
基金
英国工程与自然科学研究理事会; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会;
关键词
ACID-BASE CATALYSIS; ACTIVE-SITE; CRYSTAL-STRUCTURE; MG2+; PHOSPHORAMIDITES; KINETICS; IONS; RNA; G8;
D O I
10.1021/jacs.9b02141
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Comparison of the secondary and three-dimensional structures of the hammerhead and pistol ribozymes reveals many close similarities, so in this work we have asked if they are mechanistically identical. We have determined a new crystal structure of the pistol ribozyme and have shown that G40 acts as general base in the cleavage reaction. The conformation in the active site ensures an in-line attack of the O2' nucleophile, and the conformation at the scissile phosphate and the position of the general base are closely similar to those in the hammerhead ribozyme. However, the two ribozymes differ in the nature of the general acid. 2'-Amino substitution experiments indicate that the general acid of the hammerhead ribozyme is the O2' of G8, while that of the pistol ribozyme is a hydrated metal ion. The two ribozymes are related but mechanistically distinct.
引用
收藏
页码:7865 / 7875
页数:11
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