Phosphate Group Is Key Regulator of Melatonin Metabolism
By Biotechdaily staff writers
Posted on 05 Nov 2003
Researchers studying the sleep-inducing hormone melatonin have developed a method to modify the enzyme responsible for the synthesis of melatonin in order to prevent its degradation.Posted on 05 Nov 2003
To study melatonin metabolism in cells, investigators at Johns Hopkins University (Baltimore, MD, USA) modified serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) through the incorporation of a nonhydrolyzable phosphoserine/threonine mimetic, phosphonomethylenealanine (Pma), at position 31 (AANAT-Pma31). The presence of the added chemical group prevented enzymes that normally inactivate AANAT from removing the phosphate at position 31. The presence of the mimetic also improved the enzyme's ability to bind to a protein known as 14-3-3, further increasing the enzyme's stability and delaying its degradation. These findings were published October 26, 2003, in the online edition of Nature Structural Biology.
"We have discovered that addition and removal of the phosphate group at this position is the key step in regulating the enzyme's stability,” explained senior author Dr. Philip Cole, professor of pharmacology and molecular sciences at Johns Hopkins University. "When this phosphate group is present, the enzyme is stable.”
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