BIOL 101 |
| 8oxodG and FapydG, the most common forms of the oxidative DNA damage share the same precursor radical adduct. In E. coli., they are both repaired by formamido-pyrimidine DNA glycosylase (Fpg). Two x-ray structures containing 8oxodG and carbo-FapydG bound with Fpg are available. Although the overall structures of these two lesions are similar, they bind to the Fpg in different conformations. Through our simulation studies we found two binding modes for 8oxodG. The syn conformation observed in the crystallographic structure of Fpg obtained from B. stearothermophilus is stabilized through interaction with a non-conserved residue. The Fpg sequence found in E. coli prefers binding of 8oxodG in the anti conformation. Standard AMBER parameters cannot reproduce the x-ray structure of carbo-FapydG/Fpg. Using quantum mechanic calculations we developed new parameters. The all-atom explicit solvent simulations using the new parameters reproduced the x-ray structure, which mimics 8oxodG's anti binding mode with detailed differences. |
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Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Division of Biological Chemistry |