1H46

The catalytic module of Cel7D from Phanerochaete chrysosporium as a chiral selector: Structural studies of its complex with the b-blocker (R)-propranolol

Summary for 1H46

• Entry DOI: 10.2210/pdb1h46/pdb
• Related: 1GPI
• Descriptor: EXOGLUCANASE I, 2-acetamido-2-deoxy-beta-D-glucopyranose, (1E,2R)-1-(ISOPROPYLIMINO)-3-(1-NAPHTHYLOXY)PROPAN-2-OL, ... (4 entities in total)
• Functional Keywords: hydrolase, cellulase, cellobiohydrolase, glycoside hydrolase, adrenergic beta-blocker, enantioselectivity, enantiomer separation
• Biological source: PHANEROCHAETE CHRYSOSPORIUM
• Total number of polymer chains: 1
• Total formula weight: 46255.68

Authors

Munoz, I.G.,Mowbray, S.L.,Stahlberg, J. (deposition date: 2002-10-03, release date: 2003-04-03, Last modification date: 2024-11-13)

Primary citation

Munoz, I.G.,Mowbray, S.L.,Stahlberg, J.
The Catalytic Module of Cel7D from Phanerochaete Chrysosporium as a Chiral Selector: Structural Studies of its Complex with the Beta Blocker (R)-Propranolol
Acta Crystallogr.,Sect.D, 59:637-, 2003

PubMed Abstract: 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.

PubMed: 12657782
DOI: 10.1107/S0907444903001938

Experimental method

X-RAY DIFFRACTION (1.52 Å)