BIOL 153 |
| Ribozymes catalyze biological reactions via strategic positioning of nucleobases. One method to probe functionality is abasic substitution, which is hypothesized to generate a cavity that accommodates an exogenous ligand that restores activity. To investigate this concept, structures of the hairpin ribozyme were determined whereby Ade38, a key catalytic residue, was removed and crystallized in the absence or presence of rescue ligand 2-aminopyridine (APy). In the absence of APy, the global fold remained intact, although two A-1 conformations were evident. A minor conformer represented the native fold (panel A), and a dominant conformer revealed a 15 Å movement to fill the abasic void. A 300-fold molar excess of APy did not alleviate A-1 occupation of the abasic pocket, whereas 800-fold excess resulted in APy intercalation between Ade9 & 10 (panel B). The results reveal conformational plasticity in the hairpin ribozyme core that accounts for both inhibitory and rescue properties of APy.
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Symposium in Honor of Perry Frey
2:00 PM-4:40 PM, Wednesday, August 22, 2007 BCEC -- 109A, Oral
Division of Biological Chemistry |
