1HU0

CRYSTAL STRUCTURE OF AN HOGG1-DNA BOROHYDRIDE TRAPPED INTERMEDIATE COMPLEX

Summary for 1HU0

• Entry DOI: 10.2210/pdb1hu0/pdb
• Related: 1EBM 1FN7
• Descriptor: 5'-D(*GP*GP*TP*AP*GP*AP*CP*CP*TP*GP*GP*AP*CP*GP*C)-3', 5'-D(*GP*CP*GP*TP*CP*CP*AP*(PED)P*GP*TP*CP*TP*AP*CP*C)-3', 8-OXOGUANINE DNA GLYCOSYLASE 1, ... (6 entities in total)
• Functional Keywords: dna repair, dna glycosylase, protein/dna, borohydride, covalent trapping, product-assisted catalysis, reaction intermediate, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleoplasm. Isoform 1A: Nucleus. Isoform 2A: Mitochondrion: O15527
• Total number of polymer chains: 3
• Total formula weight: 45633.23

Authors

Fromme, J.C.,Bruner, S.D.,Yang, W.,Karplus, M.,Verdine, G.L. (deposition date: 2001-01-03, release date: 2003-02-25, Last modification date: 2024-10-30)

Primary citation

Fromme, J.C.,Bruner, S.D.,Yang, W.,Karplus, M.,Verdine, G.L.
Product-Assisted Catalysis in base-excision DNA Repair
Nat.Struct.Biol., 10:204-211, 2003

PubMed Abstract: 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.

PubMed: 12592398
DOI: 10.1038/nsb902

Experimental method

X-RAY DIFFRACTION (2.35 Å)