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MOTIVATION Functional annotation of unknown proteins is a major goal in proteomics. A key annotation is the prediction of a protein's subcellular localization. Numerous prediction techniques have been developed, typically focusing on a single underlying biological aspect or predicting a subset of all possible localizations. An important step is taken(More)
We have investigated the influence of substrate binding on the zinc ion affinity of representatives from the three metallo-beta-lactamase subclasses, B1 (BcII from Bacillus cereus and BlaB from Chryseobacterium meningosepticum), B2 (CphA from Aeromonas hydrophila), and B3 (L1 from Stenotrophomonas maltophilia). By competition experiments with metal-free(More)
d- and l-captopril are competitive inhibitors of metallo-beta-lactamases. For the enzymes from Bacillus cereus (BcII) and Aeromonas hydrophila (CphA), we found that the mononuclear enzymes are the favored targets for inhibition. By combining results from extended x-ray absorption fine structure, perturbed angular correlation of gamma-rays spectroscopy, and(More)
The performance of the AutoDock, GOLD and FlexX docking programs was evaluated for docking of dicarboxylic acid inhibitors into metallo-beta-lactamases (MBLs). GOLD provided the best overall performance, with RMSDs between experimental and docked structures of 1.8-2.6 A and a good correlation between the experimentally determined MBL-inhibitor affinities(More)
The use of substrate analogues as inhibitors provides a way to understand and manipulate enzyme function. Here we report two 1 A resolution crystal structures of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl sulfoxide and isobutyramide. Both structures present a dynamic state of inhibition. In the dimethyl sulfoxide complex(More)
Extended x-ray absorption fine structure (EXAFS) spectroscopy was combined with thermodynamic and kinetic approaches to investigate zinc binding to a zinc finger (C2H2) and a tetrathiolate (C4) peptide. Both peptides represent structural zinc sites of proteins and rapidly bind a single zinc ion with picomolar dissociation constants. In competition with EDTA(More)
Functional annotation of unknown proteins is a major goal in proteomics. A key step in this annotation process is the definition of a protein's subcellular lo-calization. As a consequence, numerous prediction techniques for localization have been developed over the years. These methods typically focus on a single underlying biological aspect or predict a(More)
We have applied pharmacophore generation, database searching, docking methodologies, and experimental enzyme kinetics to discover new structures for design of di-zinc metallo-beta-lactamase inhibitors. Based on crystal structures of class B1 metallo-beta-lactamases with a succinic acid and a mercapto-carboxylic acid inhibitor bound to the enzyme, two(More)