UDP-glucose 6-dehydrogenase

Definition:

Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans. Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity). Required for proper brain and neuronal development.

References:

[1]. Sigrid Egger, et al. Structure and mechanism of human UDP-glucose 6-dehydrogenase. J Biol Chem. 2011 Jul 8;286(27):23877-87. [Content Brief]

[2]. Nathaniel R Beattie, et al. Allostery and Hysteresis Are Coupled in Human UDP-Glucose Dehydrogenase. Biochemistry. 2017 Jan 10;56(1):202-211. [Content Brief]

[3]. Nicholas D Keul, et al. The entropic force generated by intrinsically disordered segments tunes protein function. Nature. 2018 Nov;563(7732):584-588. [Content Brief]

[4]. Nathaniel R Beattie, et al. Hysteresis and Allostery in Human UDP-Glucose Dehydrogenase Require a Flexible Protein Core. Biochemistry. 2018 Dec 18;57(50):6848-6859. [Content Brief]

[5]. Nicholas C Sennett, et al. Conformational flexibility in the allosteric regulation of human UDP-α-D-glucose 6-dehydrogenase. Biochemistry. 2011 Nov 8;50(44):9651-63. [Content Brief]

[6]. Holger Hengel, et al. Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy. Nat Commun. 2020 Jan 30;11(1):595. [Content Brief]

[7]. Nicholas C Sennett, et al. Cofactor binding triggers a molecular switch to allosterically activate human UDP-α-D-glucose 6-dehydrogenase. Biochemistry. 2012 Nov 20;51(46):9364-74. [Content Brief]

[8]. Renuka Kadirvelraj, et al. Hysteresis in human UDP-glucose dehydrogenase is due to a restrained hexameric structure that favors feedback inhibition. Biochemistry. 2014 Dec 30;53(51):8043-51. [Content Brief]

[9]. Sigrid Egger, et al. Structural and kinetic evidence that catalytic reaction of human UDP-glucose 6-dehydrogenase involves covalent thiohemiacetal and thioester enzyme intermediates. J Biol Chem. 2012 Jan 13;287(3):2119-29. [Content Brief]

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