Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket

Autor: Dirk Bebenroth, Eric Westhof, Andres Jäschke, Burckhard Seelig, Sonja Keiper
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