Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors Journal Article

Authors: Lux, M. C.; Standke, L. C.; Tan, D. S.
Article Title: Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors
Abstract: Adenylate-forming enzymes are a mechanistic superfamily that are involved in diverse biochemical pathways. They catalyze ATP-dependent activation of carboxylic acid substrates as reactive acyl adenylate (acyl-AMP) intermediates and subsequent coupling to various nucleophiles to generate ester, thioester, and amide products. Inspired by natural products, acyl sulfonyladenosines (acyl-AMS) that mimic the tightly bound acyl-AMP reaction intermediates have been developed as potent inhibitors of adenylate-forming enzymes. This simple yet powerful inhibitor design platform has provided a wide range of biological probes as well as several therapeutic lead compounds. Herein, we provide an overview of the nine structural classes of adenylate-forming enzymes and examples of acyl-AMS inhibitors that have been developed for each. © 2019, The Author(s).
Keywords: unclassified drug; review; nonhuman; ubiquitin protein ligase; enzyme activation; enzyme inhibitor; enzyme activity; drug design; drug mechanism; adenosine triphosphate; natural product; amino acid transfer rna ligase; biotin; ligase; firefly luciferase; adenylation; long chain fatty acid coenzyme a ligase; ligase inhibitor; sulfone derivative; adenosine derivative; human; priority journal; hydrolase inhibitor; adenylate forming enzyme inhibitor; biotin protein ligase; biotin protein ligase inhibitor; biow acyl coa synthetase; carbamoyltransferase; class i amino acid transfer rna ligase inhbitoe; class ii amino acid transfer rna ligase inhibitor; inorganic pyrophosphatase; long chain fatty acid coenzyme a ligase inhibitor; n type atp pyrophosphatase; n type atp pyrophosphatase inhibitor; nrps independent siderophore synthetase; ubiquitin family e1 activating enzyme inhibitor; ubiquitin protein ligase e1; yrdc like carbamoyltransferase
Journal Title: Journal of Antibiotics
Volume: 72
Issue: 6
ISSN: 0021-8820
Publisher: Nature Publishing Group  
Date Published: 2019-06-01
Start Page: 325
End Page: 349
Language: English
DOI: 10.1038/s41429-019-0171-2
PUBMED: 30982830
PROVIDER: scopus
PMCID: PMC6594144
Notes: Review -- Export Date: 3 June 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Derek S Tan
    74 Tan
  2. Michaelyn C Lux
    3 Lux