Cook, Ian; Cacace, Mary; Wang, Ting; Darrah, Kristie; Deiters, Alexander; Leyh, Thomas S. published the artcile< Small-molecule control of neurotransmitter sulfonation>, COA of Formula: C7H6BrNO, the main research area is dopamine metabolite neurotransmitter sulfonation; SULT1A3; allosteric; catecholamine; human mammary epithelial cells; inhibitor; molecular dynamics; neurotransmitter; structure activity relationship; sulfotransferase.
Controlling unmodified serotonin levels in brain synapses is a primary objective when treating major depressive disorder-a disease that afflicts ∼20% of the world′s population. Roughly 60% of patients respond poorly to first-line treatments and thus new therapeutic strategies are sought. To this end, we have constructed isoform-specific inhibitors of the human cytosolic sulfotransferase 1A3 (SULT1A3)-the isoform responsible for sulfonating ∼80% of the serotonin in the extracellular brain fluid. The inhibitor design includes a core ring structure, which anchors the inhibitor into a SULT1A3-specific binding pocket located outside the active site, and a side chain crafted to act as a latch to inhibit turnover by fastening down the SULT1A3 active-site cap. The inhibitors are allosteric, they bind with nanomolar affinity and are highly specific for the 1A3 isoform. The cap-stabilizing effects of the latch can be accurately calculated and are predicted to extend throughout the cap and into the surrounding protein. A free-energy correlation demonstrates that the percent inhibition at saturating inhibitor varies linearly with cap stabilization – the correlation is linear because the rate-limiting step of the catalytic cycle, nucleotide release, scales linearly with the fraction of enzyme in the cap-open form. Inhibitor efficacy in cultured cells was studied using a human mammary epithelial cell line that expresses SULT1A3 at levels comparable with those found in neurons. The inhibitors perform similarly in ex vivo and in vitro studies; consequently, SULT1A3 turnover can now be potently suppressed in an isoform-specific manner in human cells.
Journal of Biological Chemistry published new progress about Allosterism. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, COA of Formula: C7H6BrNO.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary