BIOL 221 |
| Ambient glucose addition reduces the O2 transport capability of hemoglobin (Hb). Consequently, significant complications arise with diabetes, where poorly controlled blood sugar can result in twice normal glycation levels. The mechanism by which glycation alters Hb function is unclear. We hypothesize interference with a functionally relevant motional dynamic in the protein. Recent NMR characterization of carbonmonoxy-Hb (HbCO) revealed a solution structure that is the average of the known solid-state structures, R and R2 [Simplaceanu, PNAS 2003]. The role of these conformations is uncertain. However, results suggested a functionally relevant R ↔ R2 equilibrium. We present results towards structural and dynamic characterization of Hb A using solution NMR, including for measure of responses to glucose addition at sites sterically relevant to the purported R ↔ R2 dynamic. This includes preparation of isotopically labeled HbCO, and a synthetic procedure for selective glycation of Hb at the N-terminus of the alpha chain. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |