Premium
Molecular Recognition at the Active Site of Catechol‐ O ‐Methyltransferase: Energetically Favorable Replacement of a Water Molecule Imported by a Bisubstrate Inhibitor
Author(s) -
Ellermann Manuel,
JakobRoetne Roland,
Lerner Christian,
Borroni Edilio,
Schlatter Daniel,
Roth Doris,
Ehler Andreas,
Rudolph Markus Georg,
Diederich François
Publication year - 2009
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200904410
Subject(s) - catechol , active site , chemistry , methyltransferase , catechol o methyl transferase , molecule , stereochemistry , biochemistry , enzyme , combinatorial chemistry , organic chemistry , gene , methylation , allele
The import business : The binding mode of highly potent bisubstrate inhibitors of catechol‐ O ‐methyltransferase (COMT) has been elucidated by X‐ray crystal structures of ternary complexes with COMT and a Mg 2+ ion (see picture). A single ligand‐imported water molecule is replaced, with a gain in binding free enthalpy of at least −1.8 kcal mol −1 compensating the costs of the energetically unfavorable conformation of the ligand in the bound state.