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Review

Specific Chemical Modification of Bacterial Type I Dehydroquinase: Opportunities for Drug Discovery

Pages 2371-2383 | Published online: 24 Nov 2015
 

Abstract

Type I dehydroquinase (DHQ1) is a class I aldolase enzyme that catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid by multistep mechanism that involves the formation of Schiff-base species. DHQ1 is present in plants and several bacterial sources but it does not have any counterpart in human cells. It has been suggested that DHQ1 may act as a virulence factor in vivo and therefore a promising target in the search for new antivirulence agents to combat widespread antibiotic resistance. This review covers recent progress in the structure-based design and chemical modifications caused by selective irreversible inhibitors. Computational studies aimed at understanding the experimentally obtained covalent modifications and inhibitory potencies of these inhibitors are also described.

Financial & competing interests disclosure

Financial support from the Spanish Ministry of Economy and Competitiveness (SAF2013-42899-R), Xunta de Galicia (GRC2013-041) and the European Regional Development Fund (ERDF) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Financial support from the Spanish Ministry of Economy and Competitiveness (SAF2013-42899-R), Xunta de Galicia (GRC2013-041) and the European Regional Development Fund (ERDF) is gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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