Cell-Effective Transition-State Analogue of Phenylethanolamine N-Methyltransferase
Niusha Mahmoodi,
Yacoba V. T. Minnow,
Rajesh K. Harijan
et al.
Abstract:Phenylethanolamine N-methyltransferase
(PNMT)
catalyzes the S-adenosyl-l-methionine (SAM)-dependent
methylation of norepinephrine to form epinephrine. Epinephrine is
implicated in the regulation of blood pressure, respiration, Alzheimer’s
disease, and post-traumatic stress disorder (PTSD). Transition-state
(TS) analogues bind their target enzymes orders of magnitude more
tightly than their substrates. A synthetic strategy for first-generation
TS analogues of human PNMT (hPNMT) permitted structural analysis of
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One-pot enzyme-catalyzed synthesis of S-adenosyl homocysteine and derivatives thereof from racemic homocysteine thiolactone and adenosine or other nucleosides provides simple and scalable access to cofactors for methyltransferase biocatalysis.
One-pot enzyme-catalyzed synthesis of S-adenosyl homocysteine and derivatives thereof from racemic homocysteine thiolactone and adenosine or other nucleosides provides simple and scalable access to cofactors for methyltransferase biocatalysis.
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