Dimitri Antoniou1, Xiaoxia Ge2, Vern L Schramm2, Steven D Schwartz1. 1. Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Blvd., Tucson, AZ 85721. 2. Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461.
Abstract
The role of protein dynamics on different time scales in enzyme catalysis remains an area of active debate. The connection between enzyme dynamics on the femtosecond time scale and transition state formation has been demonstrated in human purine nucleoside phosphorylase (PNP) through the study of a mass-altered enzyme. Isotopic substitution in human PNP (heavy PNP) decreased the rate of on-enzyme chemistry but did not alter either the transition state structure or steady-state kinetic parameters. Here we investigate the underlying atomic motions associated with altered barrier crossing probability for heavy PNP. Transition path sampling was employed to illuminate the molecular differences between barrier crossing in light and heavy enzymes. The mass effect is apparent in promoting vibrations that polarize the N-ribosidic bond, and that promote the stability of the purine leaving group. These motions facilitate barrier crossing.
The role of protein dynamics on different time scales in enzyme catalysis remains an area of active debate. The connection between enzyme dynamics on the femtosecond time scale and transition state formation has been demonstrated in humann class="Gene">purine nucleoside phosphorylase (PNP) through the study of a mass-altered enzyme. Isotopic substitution in humanPNP (heavy PNP) decreased the rate of on-enzyme chemistry but did not alter either the transition state structure or steady-state kinetic parameters. Here we investigate the underlying atomic motions associated with altered barrier crossing probability for heavy PNP. Transition path sampling was employed to illuminate the molecular differences between barrier crossing in light and heavy enzymes. The mass effect is apparent in promoting vibrations that polarize the N-ribosidic bond, and that promote the stability of the purine leaving group. These motions facilitate barrier crossing.
Authors: B R Brooks; C L Brooks; A D Mackerell; L Nilsson; R J Petrella; B Roux; Y Won; G Archontis; C Bartels; S Boresch; A Caflisch; L Caves; Q Cui; A R Dinner; M Feig; S Fischer; J Gao; M Hodoscek; W Im; K Kuczera; T Lazaridis; J Ma; V Ovchinnikov; E Paci; R W Pastor; C B Post; J Z Pu; M Schaefer; B Tidor; R M Venable; H L Woodcock; X Wu; W Yang; D M York; M Karplus Journal: J Comput Chem Date: 2009-07-30 Impact factor: 3.376
Authors: A Fedorov; W Shi; G Kicska; E Fedorov; P C Tyler; R H Furneaux; J C Hanson; G J Gainsford; J Z Larese; V L Schramm; S C Almo Journal: Biochemistry Date: 2001-01-30 Impact factor: 3.162
Authors: Ioanna Zoi; Javier Suarez; Dimitri Antoniou; Scott A Cameron; Vern L Schramm; Steven D Schwartz Journal: J Am Chem Soc Date: 2016-03-08 Impact factor: 15.419
Authors: Alan F Scott; Joel Cresser-Brown; Thomas L Williams; Pierre J Rizkallah; Yi Jin; Louis Y-P Luk; Rudolf K Allemann Journal: Appl Environ Microbiol Date: 2019-07-18 Impact factor: 4.792