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• W2029528088 abstract "Proenkephalin (PE) is a prohormone containing dibasic sites that are cleaved by proteases to generate peptide neurotransmitters and hormones. Little is known about the conformational features of such protease cleavage sites within prohormone substrates. Therefore, the goal of this study was to investigate the relative accessibilities of multiple dibasic processing sites of PE by peptide amide hydrogen-deuterium exchange mass spectrometry (DXMS). DXMS demonstrated differences in the relative accessibilities of the KR, KK, and RR cleavage sites of PE to the aqueous environment. DXMS assesses relative rates of exchange of hydrogens of the polypeptide backbone of PE with deuterium atoms from D(2)O (heavy water) in solvent. Analyses of peptides spanning each of the 12 dibasic PE cleavage sites illustrated differences in H-D exchange rates that reflect relative solvent accessibility. The mid-domain cleavage sites (dibasic sites 4-8) exhibited greater accessibility to the aqueous solvent compared to regions of the NH(2) and COOH domains (dibasic sites 2, 3, and 9-11, respectively). The NH(2)- and COOH-terminal domains both exhibited relatively high H-D exchange rates. The hydrogen exchange rate profile of PE, as well as its circular dichroism (CD) features for secondary structure, was modified in trifluoroethanol, an organic solvent that represents a more hydrophobic environment. These findings suggest that the dibasic protease cleavage sites of the PE prohormone with differences in accessibility to the aqueous environment undergo proteolytic processing to generate active neuropeptides for cell-cell communication in neuroendocrine systems." @default.
• W2029528088 created "2016-06-24" @default.
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• W2029528088 date "2009-01-27" @default.
• W2029528088 modified "2023-09-26" @default.
• W2029528088 title "Differential Accessibilities of Dibasic Prohormone Processing Sites of Proenkephalin to the Aqueous Environment Revealed by H−D Exchange Mass Spectrometry" @default.
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• W2029528088 doi "https://doi.org/10.1021/bi801888j" @default.
• W2029528088 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2752437" @default.
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