Apr 10, 2020

Phosphorylation of Threonine 107 by Calcium/Calmodulin dependent Kinase II δ Regulates the Detoxification Efficiency and Proteomic Integrity of Glyoxalase 1

BioRxiv : the Preprint Server for Biology
Jakob MorgernsternT. Fleming

Abstract

The glyoxalase system is a ubiquitously expressed enzyme system with narrow substrate specificity and is responsible for the detoxification of harmful methylglyoxal, a by-product of metabolism. Glo1 is the rate limiting enzyme of this protective system. In this study it was shown that phosphorylation of threonine-107, mediated by CamKII{delta}, is associated with elevated catalytic efficiency of Glo1. In fact, the kinetics of phosphorylated Glo1 was associated with increased Vmax and decreased Km, whereas the non-phosphorylatable Glo1 showed significantly lower Vmax and increased Km. This was also confirmed with human recombinant Glo1. Additionally, proteasomal degradation of non-phosphorylated Glo1 via ubiquitination occurred more rapidly as compared to native Glo1. The absence of the responsible kinase CamKII{delta} was associated with poor MG detoxification capacity and decreased protein content of Glo1 in a murine CamKII{delta} knock-out model. Furthermore, this regulatory mechanism is also related to an altered Glo1 status in cancer, diabetes and during aging. In summary, phosphorylation of threonine-107 in the Glo1 protein by CamKII{delta} is a quick and precise mechanism regulating Glo1 activity.

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Mentioned in this Paper

Immune System
Adaptation
Pathogenic Organism
Clustered Regularly Interspaced Short Palindromic Repeats

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