1h46
From Proteopedia
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==Overview== | ==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)., ... | + | 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== | ==About this Structure== | ||
| - | 1H46 is a | + | 1H46 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Phanerochaete_chrysosporium Phanerochaete chrysosporium] with NAG and RNP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cellulose_1,4-beta-cellobiosidase Cellulose 1,4-beta-cellobiosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.91 3.2.1.91] Structure known Active Site: NAG. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H46 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: glycoside hydrolase]] | [[Category: glycoside hydrolase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:10:28 2007'' |
Revision as of 12:05, 5 November 2007
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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 NAG and RNP as ligands. Active as Cellulose 1,4-beta-cellobiosidase, with EC number 3.2.1.91 Structure known Active Site: NAG. 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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