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| | <StructureSection load='5vsj' size='340' side='right'caption='[[5vsj]], [[Resolution|resolution]] 2.46Å' scene=''> | | <StructureSection load='5vsj' size='340' side='right'caption='[[5vsj]], [[Resolution|resolution]] 2.46Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vsj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Strco Strco]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vsj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VSJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HV:{2-[(2R,3R,4R,5R)-3-(alpha-D-glucopyranosyloxy)-4-hydroxy-2,5-bis(hydroxymethyl)pyrrolidin-1-yl]ethyl}phosphonic+acid'>9HV</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.456Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vt4|5vt4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9HV:{2-[(2R,3R,4R,5R)-3-(alpha-D-glucopyranosyloxy)-4-hydroxy-2,5-bis(hydroxymethyl)pyrrolidin-1-yl]ethyl}phosphonic+acid'>9HV</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glgE1, pep1, pep1A, pep1I, SCO5443, SC6A11.19c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=100226 STRCO])</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=5vsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsj OCA], [https://pdbe.org/5vsj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vsj RCSB], [https://www.ebi.ac.uk/pdbsum/5vsj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsj 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=5vsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsj OCA], [http://pdbe.org/5vsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vsj RCSB], [http://www.ebi.ac.uk/pdbsum/5vsj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsj 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: Strco]]
| + | [[Category: Petit C]] |
| - | [[Category: Petit, C]] | + | [[Category: Ronning DR]] |
| - | [[Category: Ronning, D R]] | + | |
| - | [[Category: 4-glucan]]
| + | |
| - | [[Category: Alpha-1]]
| + | |
| - | [[Category: Maltosyltransferase]]
| + | |
| - | [[Category: Streptomyces coelicolor]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transition state analogue]]
| + | |
| 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
We synthesized and evaluated new zwitterionic inhibitors against glycoside hydrolase-like phosphorylase Streptomyces coelicolor (Sco) GlgEI-V279S which plays a role in alpha-glucan biosynthesis. Sco GlgEI-V279S serves as a model enzyme for validated anti-tuberculosis (TB) target Mycobacterium tuberculosis (Mtb) GlgE. Pyrrolidine inhibitors 5 and 6 were designed based on transition state considerations and incorporate a phosphonate on the pyrrolidine moiety to expand the interaction network between the inhibitor and the enzyme active site. Compounds 5 and 6 inhibited Sco GlgEI-V279S with Ki = 45 +/- 4 muM and 95 +/- 16 muM, respectively, and crystal structures of Sco GlgE-V279S-5 and Sco GlgE-V279S-6 were obtained at a 3.2 A and 2.5 A resolution, respectively.
Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S.,Veleti SK, Petit C, Ronning DR, Sucheck SJ Org Biomol Chem. 2017 May 10;15(18):3884-3891. doi: 10.1039/c7ob00388a. PMID:28422240[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
- ↑ Veleti SK, Petit C, Ronning DR, Sucheck SJ. Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S. Org Biomol Chem. 2017 May 10;15(18):3884-3891. doi: 10.1039/c7ob00388a. PMID:28422240 doi:http://dx.doi.org/10.1039/c7ob00388a
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