Journal:Acta Cryst F:S2053230X20004343

Structure of Mycobacterium smegmatis α-maltose-1-phosphate synthase GlgM

Karl Syson, Clare E. M. Stevenson, David M. Lawson and Stephen Bornemann ^[1]

Molecular Tour
Mycobacterium tuberculosis is the causative agent of tuberculosis in humans. The bacterium coats itself a glycogen-like alpha-glucan to help evade an immune response. Rather than use the well-known classical biosynthetic pathway for glycogen biosynthesis requiring GlgA glycogen synthase, this pathogen uses a recently discovered alternative pathway. The alternative GlgE pathway uses a different building block to the classical pathway. We have solved the first structure of a carbohydrate-active enzyme enzymes that generates this alternative maltose-1-phosphate building block in mycobacteria from ADP-glucose and glucose-1-phosphate.

The structure of Mycobacterium smegmatis GlgM has the expected glycosyltransferase B fold for a glycosyltransferase family 4 member. GlgM is dimeric both in solution and within the crystal. . GlgM shares many structural features with other glycosyltransferase enzymes, despite the highest sequence identity with known homologous structures being only 28%. For example, many of the amino acid side chains responsible for binding the donor substrate, ADP-glucose, are in common with members of the glycosyltransferase 5 family. These include bacterial GlgA glycogen synthases, which are absent from mycobacteria.

The next step will be to see how GlgM binds glucose-1-phosphate, its acceptor substrate, and how this differs from how GlgA binds it acceptor, glycogen.

. The structures were superposed on the C-terminal domain and thus emphasize the shift in the N-terminal domain, which is indicated by the two-headed magenta arrow; the magenta asterisk marks the approximate pivot point.

References

1. ↑ Syson K, Stevenson CEM, Lawson DM, Bornemann S. Structure of the Mycobacterium smegmatis alpha-maltose-1-phosphate synthase GlgM. Acta Crystallogr F Struct Biol Commun. 2020 Apr 1;76(Pt 4):175-181. doi:, 10.1107/S2053230X20004343. Epub 2020 Apr 3. PMID:32254051 doi:http://dx.doi.org/10.1107/S2053230X20004343