Investigation of the Role of the Histidine-Aspartate Pair in the Human Exonuclease III-like Abasic Endonuclease, Ape1
- BATTELLE (PACIFIC NW LAB)
- PNNL
- OFFICE OF FELLOWSHIP PROG
- National Institute of Aging
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 pKa 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 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 studies within suggest that the Ape1 His- Asp pair functions as neither a general base catalyst nor a metal ligand. Rather, the pair likely stabilizes the pentavalent transition state necessary for phospho-transfer.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC06-76RL01830
- OSTI ID:
- 15003871
- Report Number(s):
- PNNL-SA-36499; ISSN 1089-8638; KP1101010; TRN: US201015%%167
- Journal Information:
- Journal of Molecular Biology , 329(2):311-322, Vol. 329, Issue 2; ISSN 0022-2836
- Country of Publication:
- United States
- Language:
- English
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