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. <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>. 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 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/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. | <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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