6grn | pdb_00006grn

CELLOBIOHYDROLASE I (CEL7A) FROM Trichoderma reesei with S-dihydroxypropranolol in the active site

spinqualitylabelsall models 6grn, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6grn is a 1 chain structure with sequence from Trichoderma reesei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CO, F9B, NAG NonStd Res: PCA Activity: Cellulose 1,4-beta-cellobiosidase (non-reducing end), with EC number 3.2.1.91 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GUX1_HYPJE] The biological conversion of cellulose to glucose generally requires three types of hydrolytic enzymes: (1) Endoglucanases which cut internal beta-1,4-glucosidic bonds; (2) Exocellobiohydrolases that cut the dissaccharide cellobiose from the non-reducing end of the cellulose polymer chain; (3) Beta-1,4-glucosidases which hydrolyze the cellobiose and other short cello-oligosaccharides to glucose. Publication Abstract from PubMed At the catalytic site for the hydrolysis of cellulose the enzyme cellobiohydrolase Cel7A binds the enantiomers of the adrenergic beta-blocker propranolol with different selectivity. Methyl-to-hydroxymethyl group modifications of propranolol, which result in higher affinity and improved selectivity, were herein studied by 1H,1H and 1H,13C scalar spin-spin coupling constants as well as utilizing the nuclear Overhauser effect (NOE) in conjunction with molecular dynamics simulations of the ligands per se, which showed the presence of all-antiperiplanar conformations, except for the one having a vicinal oxygen-oxygen arrangement governed by the gauche effect. For the ligand-protein complexes investigated by NMR spectroscopy using, inter alia, transferred NOESY and saturation-transfer difference (STD) NMR experiments the (S)-isomers were shown to bind with a higher affinity and a conformation similar to that preferred in solution, in contrast to the (R)-isomer. The fact that the (S)-form of the propranolol enantiomer is pre-arranged for binding to the protein is also observed for a crystal structure of dihydroxy-(S)-propranolol and Cel7A presented herein. Whereas the binding of propranolol is entropy driven the complexation with the dihydroxy analogue is anticipated to be favored also by an enthalpic term, like for its enantiomer, because of hydrogen bond donation replacing the corresponding ones from hydroxyl groups in glucosyl residues of the natural substrate. Enantioselective Binding of Propranolol and Analogues thereof to Cellobiohydrolase Cel7A.,Hamark C, Pendrill R, Landstrom J, Dotson Fagerstrom A, Sandgren M, Stahlberg J, Widmalm G Chemistry. 2018 Sep 26. doi: 10.1002/chem.201803104. PMID:30255965 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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