Product-assisted catalysis in base-excision DNA repair

Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of c...

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Veröffentlicht in:Nature structural & molecular biology 2003-03, Vol.10 (3), p.204-211
Hauptverfasser: Verdine, Gregory L, Fromme, J. Christopher, Bruner, Steven D, Yang, Wei, Karplus, Martin
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container_title Nature structural & molecular biology
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creator Verdine, Gregory L
Fromme, J. Christopher
Bruner, Steven D
Yang, Wei
Karplus, Martin
description Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of catalyzing no fewer than five sequential reaction steps using a single active site has been unknown. To help answer this, we report the structure of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine DNA glycosylase. This structure and supporting biochemical results reveal that the enzyme sequesters the excised lesion base and exploits it as a cofactor to participate in catalysis. To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction.
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identifier ISSN: 1072-8368
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subjects Amino Acid Substitution
Base Pairing
Biochemistry
Biological Microscopy
Biomedical and Life Sciences
Borohydrides - chemistry
Catalysis
Deoxyribonucleic acid
DNA
DNA Repair - physiology
DNA-Formamidopyrimidine Glycosylase
Guanine - analogs & derivatives
Guanine - chemistry
Guanine - metabolism
Imaging, Three-Dimensional
Lesions
Life Sciences
Lysine - chemistry
Lysine - metabolism
Membrane Biology
Models, Molecular
N-Glycosyl Hydrolases - chemistry
N-Glycosyl Hydrolases - genetics
N-Glycosyl Hydrolases - metabolism
Protein Conformation
Protein Structure
Schiff Bases - chemistry
Schiff Bases - metabolism
title Product-assisted catalysis in base-excision DNA repair
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