Chemogenomics of pyridoxal 5′-phosphate dependent enzymes. (February 2013)

• Record Type: Journal Article
• Authors: Singh, Ratna; Spyrakis, Francesca; Cozzini, Pietro; Paiardini, Alessandro; Pascarella, Stefano; Mozzarelli, Andrea
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 28:Number 1(2013:Feb.)
• Page Start: 183
• Page End: 194
• Publication Date: 2013-02
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2011.643305
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Pyridoxal 5′-phosphate (PLP) dependent enzymes comprise a large family that plays key roles in amino acid metabolism and are acquiring an increasing interest as drug targets. For the identification of compounds inhibiting PLP-dependent enzymes, a chemogenomics-based approach has been adopted in this work. Chemogenomics exploits the information coded in sequences and three-dimensional structures to define pharmacophore models. The analysis was carried out on a dataset of 65 high-resolution PLP-dependent enzyme structures, including representative members of four-fold types. Evolutionarily conserved residues relevant to coenzyme or substrate binding were identified on the basis of sequence-structure comparisons. A dataset was obtained containing the information on conserved residues at substrate and coenzyme binding site for each representative PLP-dependent enzyme. By linking coenzyme and substrate pharmacophores, bifunctional pharmacophores were generated that will constitute the basis for future development of small inhibitors targeting specific PLP-dependent enzymes.</p> </abstract>