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| | <StructureSection load='4u3c' size='340' side='right'caption='[[4u3c]], [[Resolution|resolution]] 3.98Å' scene=''> | | <StructureSection load='4u3c' size='340' side='right'caption='[[4u3c]], [[Resolution|resolution]] 3.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u3c]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U3C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U3C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u3c]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U3C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CEY:ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSE'>CEY</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene>, <scene name='pdbligand=PRD_900035:alpha-maltohexaose'>PRD_900035</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u2y|4u2y]], [[4u2z|4u2z]], [[4u31|4u31]], [[4u33|4u33]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4u3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u3c OCA], [https://pdbe.org/4u3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u3c RCSB], [https://www.ebi.ac.uk/pdbsum/4u3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u3c ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glgE, MT1369 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Starch_synthase_(maltosyl-transferring) Starch synthase (maltosyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.99.16 2.4.99.16] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u3c OCA], [http://pdbe.org/4u3c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u3c RCSB], [http://www.ebi.ac.uk/pdbsum/4u3c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u3c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLGE_MYCTO GLGE_MYCTO]] Essential maltosyltransferase that uses maltose 1-phosphate (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-glucans. Maltooligosaccharides with a degree of polymerization (DP) superior or equal to 4 are efficient acceptors, with DP5 being optimal in the GlgE-catalyzed polymerization with M1P. Is specific for the alpha-anomer of M1P as substrate, since the beta-anomer of M1P gives no activity. Exhibits an alpha-retaining catalytic mechanism. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB (By similarity). | + | [https://www.uniprot.org/uniprot/GLGE_MYCTO GLGE_MYCTO] Essential maltosyltransferase that uses maltose 1-phosphate (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-glucans. Maltooligosaccharides with a degree of polymerization (DP) superior or equal to 4 are efficient acceptors, with DP5 being optimal in the GlgE-catalyzed polymerization with M1P. Is specific for the alpha-anomer of M1P as substrate, since the beta-anomer of M1P gives no activity. Exhibits an alpha-retaining catalytic mechanism. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mycto]] | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: Lindenberger, J J]] | + | [[Category: Lindenberger JJ]] |
| - | [[Category: Ronning, D R]] | + | [[Category: Ronning DR]] |
| - | [[Category: Docking complex maltohexaose maltosyl transferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GLGE_MYCTO Essential maltosyltransferase that uses maltose 1-phosphate (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-glucans. Maltooligosaccharides with a degree of polymerization (DP) superior or equal to 4 are efficient acceptors, with DP5 being optimal in the GlgE-catalyzed polymerization with M1P. Is specific for the alpha-anomer of M1P as substrate, since the beta-anomer of M1P gives no activity. Exhibits an alpha-retaining catalytic mechanism. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB (By similarity).
Publication Abstract from PubMed
GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched alpha-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 A and 4.0 A, respectively. The maltohexaose structure reveals a dominant site for alpha-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with alpha-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 A resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-alpha-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 A resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.
Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors.,Lindenberger JJ, Kumar Veleti S, Wilson BN, Sucheck SJ, Ronning DR Sci Rep. 2015 Aug 6;5:12830. doi: 10.1038/srep12830. PMID:26245983[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lindenberger JJ, Kumar Veleti S, Wilson BN, Sucheck SJ, Ronning DR. Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors. Sci Rep. 2015 Aug 6;5:12830. doi: 10.1038/srep12830. PMID:26245983 doi:http://dx.doi.org/10.1038/srep12830
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