PMID: 11325593Apr 28, 2001Paper

Mechanistic studies on the alkyltransferase activity of serotonin N-acetyltransferase

Chemistry & Biology
Weiping ZhengP A Cole

Abstract

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) catalyzes the first, rate-limiting step in the biosynthesis of the circadian hormone melatonin (5-methoxy-N-acetyltryptamine) from serotonin. Our recent discovery that, in addition to catalyzing the acetyl transfer from acetyl-coenzyme A (acetyl-CoASH) to serotonin, AANAT is also a robust catalyst for the alkyl transfer reaction between CoASH and N-bromoacetyltryptamine has not only opened up a new way to develop cell-permeable AANAT acetyltransferase inhibitors that are valuable in vivo tools in helping elucidate melatonin's (patho)physiological roles, but has also raised a question - how does AANAT accelerate the alkyl transfer reaction? In this study, mechanistic aspects of the AANAT-catalyzed alkyl transfer reaction were explored by employing CoASH and a series of N-haloacetyltryptamines that were also evaluated for their AANAT acetyltransferase inhibitory activities. Investigation of various N-haloacetyltryptamine analogs showed a similar leaving group effect on the enzymatic and non-enzymatic reaction rates. Steady-state kinetic analyses demonstrated that AANAT alkyltransferase obeys a sequential, ternary complex mechanism, with random substrate bin...Continue Reading

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Citations

Apr 26, 2003·Current Opinion in Chemical Biology·Shelley D Copley
Jun 24, 2008·Journal of Toxicology and Environmental Health. Part a·Brunhilde BlomekeHermann C Roemer
Jun 23, 2012·PloS One·Xian-Ying ChengZhi-Liang Ji
May 2, 2013·ACS Chemical Neuroscience·Lucy B DissBhavik Anil Patel
Sep 22, 2018·Journal of Cellular Physiology·Bagher FarhoodAmirhossein Sahebkar
Apr 10, 2003·Journal of Enzyme Inhibition and Medicinal Chemistry·N BeaurainS Yous
Mar 9, 2002·The Journal of Biological Chemistry·Kara A ScheibnerPhilip A Cole
Dec 8, 2004·Archives of Biochemistry and Biophysics·Matthew W VettingJohn S Blanchard
Mar 4, 2010·Journal of Chemical Information and Modeling·Alban LepailleurSylvain Rault
Dec 26, 2009·Biophysical Chemistry·Maria SuarezAlfonso Jaramillo

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