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8d6k

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Sco GlgEI-V279S in complex with cyclohexyl carbasugar

Structural highlights

8d6k is a 2 chain structure with sequence from Streptomyces coelicolor A3(2). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.73Å
Ligands:	,
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

C7/C8-cyclitols and C7N-aminocyclitols find applications in the pharmaceutical sector as alpha-glucosidase inhibitors and in the agricultural sector as fungicides and insecticides. In this study, we identified C7/C8-cyclitols and C7N-aminocyclitols as potential inhibitors of Streptomyces coelicolor (Sco) GlgEI-V279S based on the docking scores. The protein and the ligand (targets 11, 12, and 13) were prepared, the states were generated at pH 7.0 +/- 2.0, and the ligands were docked into the active sites of the receptor via Glide. The synthetic route to these targets was similar to our previously reported route used to obtain 4--glucoside of valienamine (AGV), except the protecting group for target 12 was a p-bromobenzyl (PBB) ether to preserve the alkene upon deprotection. While compounds 11-13 did not inhibit Sco GlgEI-V279S at the concentrations evaluated, an X-ray crystal structure of the Sco GlgE1-V279S/13 complex was solved to a resolution of 2.73 A. This structure allowed assessment differences and commonality with our previously reported inhibitors and was useful for identifying enzyme-compound interactions that may be important for future inhibitor development. The Asp 394 nucleophile formed a bidentate hydrogen bond interaction with the exocyclic oxygen atoms (C(3)-OH and C(7)-OH) similar to the observed interactions with the Sco GlgEI-V279S in a complex with AGV (PDB:7MGY). In addition, the data suggest replacing the cyclohexyl group with more isosteric and hydrogen bond-donating groups to increase binding interactions in the + 1 binding site.

Synthesis of C7/C8-cyclitols and C7N-aminocyclitols from maltose and X-ray crystal structure of Streptomyces coelicolor GlgEI V279S in a complex with an amylostatin GXG-like derivative.,Thanvi R, Jayasinghe TD, Kapil S, Obadawo BS, Ronning DR, Sucheck SJ Front Chem. 2022 Sep 9;10:950433. doi: 10.3389/fchem.2022.950433. eCollection, 2022. PMID:36157042^[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
↑ Thanvi R, Jayasinghe TD, Kapil S, Obadawo BS, Ronning DR, Sucheck SJ. Synthesis of C7/C8-cyclitols and C7N-aminocyclitols from maltose and X-ray crystal structure of Streptomyces coelicolor GlgEI V279S in a complex with an amylostatin GXG-like derivative. Front Chem. 2022 Sep 9;10:950433. doi: 10.3389/fchem.2022.950433. eCollection, 2022. PMID:36157042 doi:http://dx.doi.org/10.3389/fchem.2022.950433

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/8d6k"

Categories: Large Structures | Jayasinghe TJ | Ronning DR

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8d6k]] 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=8D6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D6K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=RT6:(1R,4S,5S,6R)-4-(cyclohexylamino)-5,6-dihydroxy-2-(hydroxymethyl)cyclohex-2-en-1-yl+alpha-D-glucopyranoside'>RT6</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]] 2.73&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=RT6:(1R,4S,5S,6R)-4-(cyclohexylamino)-5,6-dihydroxy-2-(hydroxymethyl)cyclohex-2-en-1-yl+alpha-D-glucopyranoside'>RT6</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=8d6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d6k OCA], [https://pdbe.org/8d6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d6k RCSB], [https://www.ebi.ac.uk/pdbsum/8d6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d6k ProSAT]</span></td></tr>
 </table>

8d6k

From Proteopedia

Current revision

Sco GlgEI-V279S in complex with cyclohexyl carbasugar

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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