Structural highlights
FunctionOGA_BACTN Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Publication Abstract from PubMedModulation of enzyme activity is a powerful means of probing cellular function and can be exploited for diverse applications. Here, we explore a method of enzyme activation where covalent tethering of a small molecule to an enzyme can increase catalytic activity (kcat/KM) up to 35-fold. Using a bacterial glycoside hydrolase, BtGH84, we demonstrate how small molecule "fragments", identified as activators in free solution, can be covalently tethered to the protein using Michael-addition chemistry. We show how tethering generates a constitutively-activated enzyme-fragment conjugate, which displays both improved catalytic efficiency and increased susceptibility to certain inhibitor classes. Structure guided modifications of the tethered fragment demonstrate how specific interactions between the fragment and the enzyme influence the extent of activation. This work suggests that a similar approach may be used to modulate the activity of enzymes such as to improve catalytic efficiency or increase inhibitor susceptibility. Increase of enzyme activity through specific covalent modification with fragments.,Darby JF, Atobe M, Firth JD, Bond P, Davies GJ, O'Brien P, Hubbard RE Chem Sci. 2017 Nov 1;8(11):7772-7779. doi: 10.1039/c7sc01966a. Epub 2017 Sep 27. PMID:29163914[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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