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NMR investigation of Tyr105 mutants in TEM-1 beta-lactamase: dynamics are correlated with function.

Abstract : The existence of coupled residue motions on various time scales in enzymes is now well accepted, and their detailed characterization has become an essential element in understanding the role of dynamics in catalysis. To this day, a handful of enzyme systems has been shown to rely on essential residue motions for catalysis, but the generality of such phenomena remains to be elucidated. Using NMR spectroscopy, we investigated the electronic and dynamic effects of several mutations at position 105 in TEM-1 beta-lactamase, an enzyme responsible for antibiotic resistance. Even in absence of substrate, our results show that the number and magnitude of short and long range effects on (1)H-(15)N chemical shifts are correlated with the catalytic efficiencies of the various Y105X mutants investigated. In addition, (15)N relaxation experiments on mutant Y105D show that several active-site residues of TEM-1 display significantly altered motions on both picosecond-nanosecond and microsecond-millisecond time scales despite many being far away from the site of mutation. The altered motions among various active-site residues in mutant Y105D may account for the observed decrease in catalytic efficiency, therefore suggesting that short and long range residue motions could play an important catalytic role in TEM-1 beta-lactamase. These results support previous observations suggesting that internal motions play a role in promoting protein function.
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Contributor : Nicolas Doucet Connect in order to contact the contributor
Submitted on : Monday, October 1, 2012 - 4:29:27 AM
Last modification on : Monday, July 20, 2020 - 1:06:04 PM

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Nicolas Doucet, Pierre-yves Savard, Joelle N Pelletier, Stéphane M Gagné. NMR investigation of Tyr105 mutants in TEM-1 beta-lactamase: dynamics are correlated with function.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2007, 282 (29), pp.21448-59. ⟨10.1074/jbc.M609777200⟩. ⟨pasteur-00736958⟩



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