Journal article
Investigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1
Journal of molecular biology, Vol.329(2), pp.311-322
05/30/2003
Handle:
https://hdl.handle.net/2376/109555
PMID: 12758078
Abstract
Hydrogen bonded histidine-aspartate (His-Asp) pairs are critical constituents in several key enzymatic reactions. To date, the role that these pairs play in catalysis is best understood in serine and trypsin-like proteases, where structural and biochemical NMR studies have revealed important pK(a) values and hydrogen bonding patterns within the catalytic pocket. However, the role of the His-Asp pair in metal-assisted catalysis is less clear. Here, we apply liquid-state NMR to investigate the role of a critical histidine residue of apurinic endonuclease 1 (Ape1), a human DNA repair enzyme that cleaves adjacent to abasic sites in DNA using one or more divalent cations and an active-site His-Asp pair. The results of these studies suggest that the Ape1 His-Asp pair does not function as either a general base catalyst or a metal ligand. Rather, the pair likely stabilizes the pentavalent transition state necessary for phospho-transfer.
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Details
- Title
- Investigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1
- Creators
- David F Lowry - Macromolecular Structure & Dynamics, Environmental Molecular Sciences Laboratory, Richland, WA 99352, USA. david.lowry@pnl.govDavid W HoytFayaz A KhaziJohn BaguAndrea G LindseyDavid M Wilson, 3rd
- Publication Details
- Journal of molecular biology, Vol.329(2), pp.311-322
- Academic Unit
- Engineering and Applied Sciences (TRIC), School of
- Publisher
- England
- Grant note
- CA79056 / NCI NIH HHS
- Identifiers
- 99900547047401842
- Language
- English
- Resource Type
- Journal article