4u2y
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Sco GlgEI-V279S in Complex with Reaction Intermediate Azasugar== | |
| + | <StructureSection load='4u2y' size='340' side='right'caption='[[4u2y]], [[Resolution|resolution]] 2.48Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4u2y]] 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=4U2Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U2Y FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.483Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RZM:(2R,3R,4R,5R)-4-HYDROXY-2,5-BIS(HYDROXYMETHYL)PYRROLIDIN-3-YL+ALPHA-D-GLUCOPYRANOSIDE'>RZM</scene></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=4u2y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2y OCA], [https://pdbe.org/4u2y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u2y RCSB], [https://www.ebi.ac.uk/pdbsum/4u2y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u2y ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == 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<ref>PMID:26245983</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4u2y" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lindenberger JJ]] | ||
| + | [[Category: Ronning DR]] | ||
Current revision
Sco GlgEI-V279S in Complex with Reaction Intermediate Azasugar
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