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. It 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.
References
- ↑ 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
