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 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 3 June 2019 -- Source: Scopus |
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