Proteins are intrinsically flexible macromolecules that undergo internal motions with time scales spanning femtoseconds to milliseconds. Site specific activation of such fluctuations within a protein scaffold is increasingly attributed to the reaction barrier for active site chemistry. Time, temperature, and mutation dependent hydrogen–deuterium exchange coupled to mass spectrometry (HDX-MS) has been used to locate such thermal networks for the deamination of adenosine to inosine and ammonia catalyzed by murine adenosine deaminase (mADA) (Gao, Shuaihua, et al. "Hydrogen–deuterium exchange within adenosine deaminase, a TIM barrel hydrolase, identifies networks for thermal activation of catalysis." JACS, 142(47), 2020: 19936-19949). This talk will focus on the detailed structural motifs of the uncovered networks that reach from protein/water interfaces to key residues within the active site, A model of enzyme catalysis will be discussed that incorporates both equilibrating conformational landscapes and site specific dynamically activated heat transfer (Supported by funds from the NIGMS).

Hydrogen deuterium exchange within adenosine deaminase provides long range protein networks and structural motifs for the thermal activation of active site chemistry

ACS Spring Meeting 2021

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