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1h46
From Proteopedia
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| , resolution 1.52Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Cellulose 1,4-beta-cellobiosidase, with EC number 3.2.1.91 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Sun Mar 30 20:57:17 2008
