N ‑(6‑Aminohexyl)‑5‑chloro‑1‑naphthalenesulfonamide, a centrin antagonist, inhibits Tb3+/peptides-binding properties.

N‑(6‑Aminohexyl)‑5‑chloro‑1‑naphthalenesulfonamide, a centrin antagonist, inhibits Tb3+/peptides-binding properties. J Inorg Biochem. 2019 Jan 11;193:15-24 Authors: Li M, Zhang W, Yang B Abstract N‑(6‑Aminohexyl)‑5‑chloro‑1‑naphthalenesulfonamide (W-7), a kind of adjuvant chemotherapy, can bind to calmodulin and inhibit Ca2+/calmodulin-regulated enzyme activities and cell proliferation. Similar to calmodulin, euplotes octocarinatus centrin (EoCen) belongs to EF-hand superfamily of calcium-binding proteins. It is associated with nucleotide excision repair (NER), cell division cycle and ciliogenesis. In the present study, the comparative interaction of W-7 with EoCen was first examined by using various spectroscopic, calorimetric methods and molecular docking. The obtain results recommend that only one W-7 molecule is identified binding to the C-terminal hydrophobic pocket of centrin that normally plays a role in anchoring targets. Methyl groups of Ala126, Met141, Ile161 and M162 of C-terminal may react with W-7 chloronaphthalene ring, other aliphatic or aromatic side-chains in a deep hydrophobic pocket of protein. Circular dichroism (CD) and fluorescence lifetime experiments reveal that W-7 triggers a conformational change of centrin. As a result, W-7 is identified to be an antagonist of centrin. It appears to inhibit the centrin-mediated activation of target proteins by blocking the hydrophobic pocket. Moreove...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research