1h46

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spinqualitylabelsall models 1h46, resolution 1.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE CATALYTIC MODULE OF CEL7D FROM PHANEROCHAETE CHRYSOSPORIUM AS A CHIRAL SELECTOR: STRUCTURAL STUDIES OF ITS COMPLEX WITH THE B-BLOCKER (R)-PROPRANOLOL

Overview

Previous investigations have shown that the major cellobiohydrolase of, Phanerochaete chrysosporium, Cel7D (CBH 58), can be used to separate the, enantiomers of a number of drugs, including adrenergic beta blockers such, as propranolol. The structural basis of this enantioselectivity is, explored here. A 1.5 A X-ray structure of the catalytic domain of Cel7D in, complex with (R)-propranolol showed the ligand bound at the active site in, glucosyl-binding subsites -1/+1. The catalytic residue Glu207 makes a, strong charge-charge interaction with the secondary amine of, (R)-propranolol; this is supported by a second interaction of the amine, with the nearby Asp209. The aromatic naphthyl group stacks onto the indole, ring of Trp373 (normally the glucosyl-binding platform of subsite +1)., Other factors also contribute to good complementarity between the ligand, and the substrate-binding cleft of the enzyme. Comparison with the, previous structure of a related cellulase, Cel7A from Trichoderma reesei, in complex with (S)-propranolol strongly suggests that these enzymes will, bind the (S)-enantiomer in a very similar manner, distinct from their mode, of binding to (R)-propranolol. Tighter binding of both enzymes to the, (S)-enantiomer is largely explained by two additional hydrogen-bonding, interactions with its hydroxyl group. The distinct preference for the, (R)-enantiomer is probably a consequence of structural differences near, the naphthyl group of the ligand.

About this Structure

1H46 is a Single protein structure of sequence from Phanerochaete chrysosporium with and as ligands. Active as Cellulose 1,4-beta-cellobiosidase, with EC number 3.2.1.91 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The catalytic module of Cel7D from Phanerochaete chrysosporium as a chiral selector: structural studies of its complex with the beta blocker (R)-propranolol., Munoz IG, Mowbray SL, Stahlberg J, Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):637-43. Epub 2003, Mar 25. PMID:12657782

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