title: Druggability of the enzymes of the non-mevalonate-pathway.
abstract: The non-mevalonate pathway constitutes a source of novel drug targets. This biosynthetic route is essential for pathogens but is absent in humans. Our systematic evaluation of the druggability of all enzymes provides a convenient way of selecting targets that should be most easily inhibited by small-molecule drugs. We found that not every target is equally druggable and we identified novel, druggable, potentially allosteric sites. These results should accelerate the development of anti-infective drugs with a novel mode of action, which are needed ever more urgently in light of the rapid emergence of drug-resistant strains.
authors.affiliation: University of Groningen, Stratingh Institute for Chemistry, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Masini
authors.forename: Blijke S
authors.initials: BS
authors.lastname: Kroezen
authors.forename: Anna K H
authors.initials: AK
authors.lastname: Hirsch
mesh_terms: D000495:Allosteric Site; D000890:Anti-Infective Agents / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000187:drug effects; D015195:Drug Design; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism; D058990:Molecular Targeted Therapy
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D004798:Enzymes; D008798:Mevalonic Acid