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4u31

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Revision as of 15:04, 15 November 2017

Sco GlgEI-V279S in Complex with maltose-C-phosphonate

Structural highlights

4u31 is a 2 chain structure with sequence from Strco. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4u2y, 4u2z, 4u33, 4u3c
Gene:	glgE1, pep1, pep1A, pep1I, SCO5443, SC6A11.19c (STRCO)
Activity:	Starch synthase (maltosyl-transferring), with EC number 2.4.99.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u31"

Categories: Strco | Lindenberger, J J | Ronning, D R | Inhibitors complex maltose-c-phosphonate maltosyl-transferase | Transferase

@@ Line 3: / Line 3: @@
 <StructureSection load='4u31' size='340' side='right' caption='[[4u31]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u31]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U31 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u31]] 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=4U31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U31 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MVP:(1S)-1,5-ANHYDRO-4-O-ALPHA-D-GLUCOPYRANOSYL-1-(PHOSPHONOMETHYL)-D-GLUCITOL'>MVP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u2y|4u2y]], [[4u2z|4u2z]], [[4u33|4u33]], [[4u3c|4u3c]]</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='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=4u31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u31 OCA], [http://pdbe.org/4u31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u31 RCSB], [http://www.ebi.ac.uk/pdbsum/4u31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u31 ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Strco]]
 [[Category: Lindenberger, J J]]
 [[Category: Ronning, D R]]
 [[Category: Inhibitors complex maltose-c-phosphonate maltosyl-transferase]]
 [[Category: Transferase]]

4u31

From Proteopedia

Revision as of 15:04, 15 November 2017

Sco GlgEI-V279S in Complex with maltose-C-phosphonate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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