Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket
Autor: | Dirk Bebenroth, Eric Westhof, Andres Jäschke, Burckhard Seelig, Sonja Keiper |
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Přispěvatelé: | Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg [Heidelberg], Institut für Chemie, Freie Universität Berlin, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2004 |
Předmět: |
Models
Molecular Clinical Biochemistry MESH: Base Sequence 01 natural sciences Biochemistry Chemical reaction Maleimides Drug Discovery Nucleotide MESH: Maleimides Anthracenes chemistry.chemical_classification 0303 health sciences biology MESH: Diethyl Pyrocarbonate MESH: Anthracenes Ribozyme MESH: Research Support N General Medicine Cycloaddition MESH: Mutagenesis Site-Directed MESH: Nucleic Acid Conformation Molecular Medicine Electrophoresis Polyacrylamide Gel MESH: Lead MESH: Models Molecular Reaction mechanism Stereochemistry Base pair Molecular Sequence Data Sulfuric Acid Esters 010402 general chemistry 03 medical and health sciences Ribonucleases Diethyl Pyrocarbonate MESH: RNA Catalytic RNA Catalytic [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology 030304 developmental biology Pharmacology Binding Sites MESH: Molecular Sequence Data Base Sequence Protein tertiary structure 0104 chemical sciences Spectrometry Fluorescence Lead chemistry MESH: Binding Sites Mutagenesis Site-Directed biology.protein Nucleic Acid Conformation Pseudoknot MESH: Electrophoresis Polyacrylamide Gel |
Zdroj: | Chem Biol Chem Biol, 2004, 11 (9), pp.1217-27. ⟨10.1016/j.chembiol.2004.06.011⟩ |
DOI: | 10.1016/j.chembiol.2004.06.011⟩ |
Popis: | Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5′ terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5′-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices. |
Databáze: | OpenAIRE |
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