Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors. Review uri icon

Overview

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.

publication date

  • April 15, 2019

Research

keywords

  • Adenosine Monophosphate
  • Enzyme Inhibitors
  • Ligases

Identity

PubMed Central ID

  • PMC6594144

Scopus Document Identifier

  • 85064511416

Digital Object Identifier (DOI)

  • 10.1038/s41429-019-0171-2

PubMed ID

  • 30982830

Additional Document Info

volume

  • 72

issue

  • 6