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| | <StructureSection load='4cn4' size='340' side='right'caption='[[4cn4]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4cn4' size='340' side='right'caption='[[4cn4]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cn4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_coelicolor"_(muller_1908)_lieske_1921 "actinomyces coelicolor" (muller 1908) lieske 1921]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CN4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cn4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CN4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=SHG:2-DEOXY-2-FLUORO-BETA-D-GLUCOPYRANOSE'>SHG</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=SHG:2-DEOXY-2-FLUORO-BETA-D-GLUCOPYRANOSE'>SHG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cn1|4cn1]], [[4cn6|4cn6]]</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=4cn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cn4 OCA], [https://pdbe.org/4cn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cn4 RCSB], [https://www.ebi.ac.uk/pdbsum/4cn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cn4 ProSAT]</span></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=4cn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cn4 OCA], [http://pdbe.org/4cn4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cn4 RCSB], [http://www.ebi.ac.uk/pdbsum/4cn4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cn4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLGE1_STRCO GLGE1_STRCO]] 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 DP6 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. Alpha-D-glucose 1-phosphate cannot serve as a donor substrate, but alpha-maltosyl fluoride is an efficient donor in vitro. Exhibits an alpha-retaining catalytic mechanism, with evidence that maltooligosaccharide acceptors are extended at their non-reducing ends. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen or maltoheptaose in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is probably involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB.<ref>PMID:21914799</ref> | + | [[https://www.uniprot.org/uniprot/GLGE1_STRCO GLGE1_STRCO]] 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 DP6 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. Alpha-D-glucose 1-phosphate cannot serve as a donor substrate, but alpha-maltosyl fluoride is an efficient donor in vitro. Exhibits an alpha-retaining catalytic mechanism, with evidence that maltooligosaccharide acceptors are extended at their non-reducing ends. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen or maltoheptaose in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is probably involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB.<ref>PMID:21914799</ref> |
| | <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: Bornemann, S]] | + | [[Category: Streptomyces coelicolor]] |
| - | [[Category: Lawson, D M]] | + | [[Category: Bornemann S]] |
| - | [[Category: Rashid, A M]] | + | [[Category: Lawson DM]] |
| - | [[Category: Saalbach, G]] | + | [[Category: Rashid AM]] |
| - | [[Category: Stevenson, C E.M]] | + | [[Category: Saalbach G]] |
| - | [[Category: Svergun, D I]] | + | [[Category: Stevenson CEM]] |
| - | [[Category: Syson, K]] | + | [[Category: Svergun DI]] |
| - | [[Category: Tang, M]] | + | [[Category: Syson K]] |
| - | [[Category: Tuukanen, A]] | + | [[Category: Tang M]] |
| - | [[Category: Withers, S G]] | + | [[Category: Tuukanen A]] |
| - | [[Category: Alpha-glucan biosynthesis]]
| + | [[Category: Withers SG]] |
| - | [[Category: Drug target]]
| + | |
| - | [[Category: Glycoside hydrolase family 13_3]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
[GLGE1_STRCO] 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 DP6 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. Alpha-D-glucose 1-phosphate cannot serve as a donor substrate, but alpha-maltosyl fluoride is an efficient donor in vitro. Exhibits an alpha-retaining catalytic mechanism, with evidence that maltooligosaccharide acceptors are extended at their non-reducing ends. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen or maltoheptaose in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is probably involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB.[1]
Publication Abstract from PubMed
GlgE (EC 2.4.99.16) is an alpha-maltose 1-phosphate:(1-->4)-alpha-d-glucan 4-alpha-d-maltosyltransferase of the CAZy glycoside hydrolase 13_3 family. It is the defining enzyme of a bacterial alpha-glucan biosynthetic pathway and is a genetically validated anti-tuberculosis target. It catalyzes the alpha-retaining transfer of maltosyl units from alpha-maltose 1-phosphate to maltooligosaccharides and is predicted to use a double-displacement mechanism. Evidence of this mechanism was obtained using a combination of site-directed mutagenesis of Streptomyces coelicolor GlgE isoform I, substrate analogues, protein crystallography, and mass spectrometry. The X-ray structures of alpha-maltose 1-phosphate bound to a D394A mutein and a beta-2-deoxy-2-fluoromaltosyl-enzyme intermediate with a E423A mutein were determined. There are few examples of CAZy glycoside hydrolase family 13 members that have had their glycosyl-enzyme intermediate structures determined, and none before now have been obtained with a 2-deoxy-2-fluoro substrate analogue. The covalent modification of Asp394 was confirmed using mass spectrometry. A similar modification of wild-type GlgE proteins from S. coelicolor and Mycobacterium tuberculosis was also observed. Small-angle X-ray scattering of the M. tuberculosis enzyme revealed a homodimeric assembly similar to that of the S. coelicolor enzyme but with slightly differently oriented monomers. The deeper understanding of the structure-function relationships of S. coelicolor GlgE will aid the development of inhibitors of the M. tuberculosis enzyme.
Structural Insight into How Streptomyces coelicolor Maltosyl Transferase GlgE Binds alpha-Maltose 1-Phosphate and Forms a Maltosyl-enzyme Intermediate.,Syson K, Stevenson CE, Rashid AM, Saalbach G, Tang M, Tuukkanen A, Svergun DI, Withers SG, Lawson DM, Bornemann S Biochemistry. 2014 Apr 22;53(15):2494-504. doi: 10.1021/bi500183c. Epub 2014 Apr , 11. PMID:24689960[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Syson K, Stevenson CE, Rejzek M, Fairhurst SA, Nair A, Bruton CJ, Field RA, Chater KF, Lawson DM, Bornemann S. Structure of a Streptomyces maltosyltransferase GlgE: a homologue of a genetically validated anti-tuberculosis target. J Biol Chem. 2011 Sep 13. PMID:21914799 doi:10.1074/jbc.M111.279315
- ↑ Syson K, Stevenson CE, Rashid AM, Saalbach G, Tang M, Tuukkanen A, Svergun DI, Withers SG, Lawson DM, Bornemann S. Structural Insight into How Streptomyces coelicolor Maltosyl Transferase GlgE Binds alpha-Maltose 1-Phosphate and Forms a Maltosyl-enzyme Intermediate. Biochemistry. 2014 Apr 22;53(15):2494-504. doi: 10.1021/bi500183c. Epub 2014 Apr , 11. PMID:24689960 doi:http://dx.doi.org/10.1021/bi500183c
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