6qwi

Structure of beta-glucosidase A from Paenibacillus polymyxa complexed with multivalent inhibitors.

spinqualitylabelsall models 6qwi, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qwi is a 2 chain structure with sequence from Paenibacillus polymyxa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.85Å Ligands: JJW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BGLA_PAEPO BglA is intracellular and cleaves cellobiose probably through inorganic phosphate mediated hydrolysis. Publication Abstract from PubMed The synthesis of multivalent pyrrolidine iminosugars via CuAAC click reaction between different pyrrolidine-azide derivatives and tri- or hexavalent alkynyl scaffolds is reported. The new multimeric compounds, together with the monomeric reference, were evaluated as inhibitors against two homologous GH1 beta-glucosidases (BglA and BglB from Paenibacillus polymyxa). The multivalent inhibitors containing an aromatic moiety in the linker between the pyrrolidine and the scaffold inhibited the octameric BglA (microM range) but did not show affinity against the monomeric BglB, despite the similarity between the active site of both enzymes. A modest multivalent effect (rp/n=12) was detected for the hexavalent inhibitor 12. Structural analysis of the complexes between the monomeric and the trimeric iminosugar inhibitors (4 and 10) and BglA showed the insertion of the inhibitors at the active site of BglA, confirming a competitive mode of inhibition as indicated by enzyme kinetics. Additionally, structural comparison of the BglA/4 complex with the reported BglB/2F-glucose complex illustrates the key determinants responsible for the inhibitory effect and explains the reasons of the inhibition of BglA and the no inhibition of BglB. Potential inhibition of other beta-glucosidases with therapeutic relevance is discussed under the light of these observations. Structural basis of the inhibition of GH1 beta-glucosidases by multivalent pyrrolidine iminosugars.,Martinez-Bailen M, Jimenez-Ortega E, Carmona AT, Robina I, Sanz-Aparicio J, Talens-Perales D, Polaina J, Matassini C, Cardona F, Moreno-Vargas AJ Bioorg Chem. 2019 Jun 4;89:103026. doi: 10.1016/j.bioorg.2019.103026. PMID:31226649 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-glucosidase 3D structures

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