Structural Biology of Nucleic-Acid Recognition and its Roles in Regulation of Protein Functions

The biochemistry and structural biology of the hammerhead ribozyme (HHR) has been well-elucidated. The secondary and tertiary structural elements that enable sugar-phosphate bond scission to be be catalyzed by this RNA are clearly understood. We have taken advantage of this knowledge base to test the extent to which synthetic molecules, may be used to trigger structure in secondary structure and tertiary interactions and thereby control HHR catalysis. These molecules belong to a family of molecules we call generally call “bPNAs” based on our work on bifacial peptide nucleic acid (bPNA). This family of molecules display the “bifacial” heterocycle melamine, which acts as a base-triple upon capturing two equivalents of thymine or uracil. Loosely structured internal oligouridylate bulges of 4-20 nucleotides can be restructured as triplex hybrid stems upon binding bPNAs. As such, a duplex stem element can be replaced with a bPNA triplex hybrid stem; similarly, a tertiary loop-stem interaction can be replaced with a loop-bPNA-stem complex. In this chapter, we discuss how bPNAs are prepared and applied to study structure-function turn-on in the hammerhead ribozyme system.

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Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

Science China Chemistry ◽

10.1007/s11426-010-4174-x ◽

2011 ◽

Vol 54 (1) ◽

pp. 3-23 ◽

Cited By ~ 10

Author(s):

JianHua Gan ◽

Jia Sheng ◽

Zhen Huang

Keyword(s):

Drug Discovery ◽

Nucleic Acid ◽

Nucleic Acids ◽

Structural Biology ◽

Protein Nucleic Acid ◽

Novel Drug

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Between Objectivity and Whim: Nucleic Acid Structural Biology

Topics in Current Chemistry - DNA Binders and Related Subjects ◽

10.1007/b100443 ◽

2005 ◽

pp. 77-88 ◽

Cited By ~ 10

Author(s):

Loren Dean Williams

Keyword(s):

Nucleic Acid ◽

Structural Biology

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Synthetic bPNAs as Allosteric Triggers of Hammerhead Ribozyme Catalysis

10.26434/chemrxiv.7680137.v1 ◽

2019 ◽

Author(s):

Dennis Bong ◽

Yufeng Liang ◽

Jie Mao

Keyword(s):

Nucleic Acid ◽

Secondary Structure ◽

Structure Function ◽

Structural Biology ◽

Peptide Nucleic Acid ◽

Hammerhead Ribozyme ◽

Structural Elements ◽

Sugar Phosphate ◽

Turn On ◽

Bond Scission

The biochemistry and structural biology of the hammerhead ribozyme (HHR) has been well-elucidated. The secondary and tertiary structural elements that enable sugar-phosphate bond scission to be be catalyzed by this RNA are clearly understood. We have taken advantage of this knowledge base to test the extent to which synthetic molecules, may be used to trigger structure in secondary structure and tertiary interactions and thereby control HHR catalysis. These molecules belong to a family of molecules we call generally call “bPNAs” based on our work on bifacial peptide nucleic acid (bPNA). This family of molecules display the “bifacial” heterocycle melamine, which acts as a base-triple upon capturing two equivalents of thymine or uracil. Loosely structured internal oligouridylate bulges of 4-20 nucleotides can be restructured as triplex hybrid stems upon binding bPNAs. As such, a duplex stem element can be replaced with a bPNA triplex hybrid stem; similarly, a tertiary loop-stem interaction can be replaced with a loop-bPNA-stem complex. In this chapter, we discuss how bPNAs are prepared and applied to study structure-function turn-on in the hammerhead ribozyme system.

Download Full-text