Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5807
Title: Homodimeric Enzymes as Drug Targets
Authors: D., Cardinale
O. M., H.
S., Ferrari
G., Ponterini
G., Cruciani
E., Carosati
A. M., Tochowicz
Mangani, Stefano 
R. C., Wade
M. P., Costi
Keywords: protein-protein interaction; multimeric complex; inhibition
Issue Date: 2010
Project: None 
Journal: CURRENT MEDICINAL CHEMISTRY
Abstract: 
Many enzymes and proteins are regulated by their quaternary structure and/or by their association in homoand/or hetero-oligomer complexes. Thus, these protein-protein interactions can be good targets for blocking or modulating protein function therapeutically. The large number of oligomeric structures in the Protein Data Bank (http://www.rcsb.org/) reflects growing interest in proteins that function as multimeric complexes. In this review, we consider the particular case of homodimeric enzymes as drug targets. There is intense interest in drugs that inhibit dimerization of a functionally obligate homodimeric enzyme. Because amino acid conservation within enzyme interfaces is often low compared to conservation in active sites, it may be easier to achieve drugs that target protein interfaces selectively and specifically. Two main types of dimerization inhibitors have been developed: peptides or peptidomimetics based on sequences involved in protein-protein interactions, and small molecules that act at hot spots in protein-protein interfaces. Examples include inhibitors of HIV protease and HIV integrase. Studying the mechanisms of action and locating the binding sites of such inhibitors requires different techniques for different proteins. For some enzymes, ligand binding is only detectable in vivo or after unfolding of the complexes. Here, we review the structural features of dimeric enzymes and give examples of inhibition through interference in dimer stability. Several techniques for studying these complex phenomena will be presented.
Description: 
47919
URI: http://hdl.handle.net/20.500.12779/5807
ISSN: 0929-8673
DOI: 10.2174/092986710790712156
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