Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 329, Issue 2, Pages 311-322Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(03)00382-6
Keywords
Ape1; His-Asp pair; NMR; DNA repair; abasic
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Funding
- NCI NIH HHS [CA79056] Funding Source: Medline
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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. (C) 2003 Elsevier Science Ltd. All rights reserved.
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