PMID:21987796

Citation	Chang, A, Singh, S, Helmich, KE, Goff, RD, Bingman, CA, Thorson, JS and Phillips, GN Jr (2011) Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity. Proc. Natl. Acad. Sci. U.S.A. 108:17649-54
Abstract	Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.
Links	PubMed PMC3203770 Online version:10.1073/pnas.1108484108
Keywords	Aminoglycosides/biosynthesis; Antibiotics, Antineoplastic/biosynthesis; Carbohydrates/chemistry; Enediynes/chemistry; Glycosyltransferases/genetics; Glycosyltransferases/metabolism; Hydroxylamines/metabolism; Protein Engineering/methods; Protein Interaction Domains and Motifs/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MICEC:Q8KNE0		GO:0016757: transferase activity, transferring glycosyl groups	ECO:0000314:		F		CalG2 is a glycosyltransferase from Micromonospora echinospora derived from the calicheamicin gene cluster. Structure of CalG2 was solved by X-ray crystallography. Fig 2 & 3 show the structure with bound substrate and the catalytic residues.	complete CACAO 8736
MICEC:Q8KNF2		GO:0016757: transferase activity, transferring glycosyl groups	ECO:0000314:		F		CalG1 is a glycosyltransferase in the calicheamicin gene cluster found in the Micromonospora echinospora organism. Its structure is solved by X-ray crystallography, as shown in Fig 2D & 3D.	complete CACAO 8738
MICEC:Q8KNC3		GO:0016757: transferase activity, transferring glycosyl groups	ECO:0000314:		F		The structure of the Glycosyltransferase isolated from Micromonospora echinospora via X-ray crystallography. The gene for the Glycosyltransferase is located on the Calicheamicin gene cluster.Structure is shown in Fig 2C and 3C.	complete CACAO 8925

References

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