Journal:Acta Cryst F:S2053230X20004343
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''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. | ''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 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. <scene name='84/840500/Cv/2'>It is a dimeric enzyme with a head-to-head configuration where the N-terminal domains form the dimer interface</scene> (PDB entry [[6tvp]]). 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 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. | ||
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| + | <scene name='84/840500/Cv/3'>The two copies of the monomer within the crystal show reveal conformations where the N and C-terminal domains move relative to each other to give open and closed forms</scene>. 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. | ||
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| + | <scene name='84/840500/Cv/6'>The ADP-glucose donor substrate binding site of the C-terminal domain shares many common amino acid side chains with homologues that use the same donor (e.g. bacterial GlgA glycogen synthases)</scene>. The conserved GlgM (cream carbons) and EcGS (grey carbons; PDB entry [[2qzs]]) donor binding site displaying a superposition of structurally equivalent key residues (labels refer to GlgM only; see main text for ''E. coli'' numbering). Also shown are the ADP and α-D-glucose (GLC) ligands (green carbons) bound to EcGS. | ||
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| + | '''PDB reference:''' GlgM, [[6tvp]]. | ||
<b>References</b><br> | <b>References</b><br> | ||
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