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Kamihira2000 - calcitonin fibrillation kinetics

ABSTRACT: Kamihira2000 - calcitonin fibrillation kinetics This model studies the kinetics of human calcitonin fibrillation described as a two-step process. Empirical data is used to determine the parameter values. Results show that the first step in fibrillation is a slow homogenous reaction and the second step is a fast autocatalytic heterogenous reaction. This model is described in the article: Conformational transitions and fibrillation mechanism of human calcitonin as studied by high-resolution solid-state 13C NMR. Kamihira M, Naito A, Tuzi S, Nosaka AY, Saitô H. Protein Sci. 2000 May; 9(5): 867-877 Abstract: Conformational transitions of human calcitonin (hCT) during fibril formation in the acidic and neutral conditions were investigated by high-resolution solid-state 13C NMR spectroscopy. In aqueous acetic acid solution (pH 3.3), a local alpha-helical form is present around Gly10 whereas a random coil form is dominant as viewed from Phe22, Ala26, and Ala31 in the monomer form on the basis of the 13C chemical shifts. On the other hand, a local beta-sheet form as viewed from Gly10 and Phe22, and both beta-sheet and random coil as viewed from Ala26 and Ala31 were detected in the fibril at pH 3.3. The results indicate that conformational transitions from alpha-helix to beta-sheet, and from random coil to beta-sheet forms occurred in the central and C-terminus regions, respectively, during the fibril formation. The increased 13C resonance intensities of fibrils after a certain delay time suggests that the fibrillation can be explained by a two-step reaction mechanism in which the first step is a homogeneous association to form a nucleus, and the second step is an autocatalytic heterogeneous fibrillation. In contrast to the fibril at pH 3.3, the fibril at pH 7.5 formed a local beta-sheet conformation at the central region and exhibited a random coil at the C-terminus region. Not only a hydrophobic interaction among the amphiphilic alpha-helices, but also an electrostatic interaction between charged side chains can play an important role for the fibril formation at pH 7.5 and 3.3 acting as electrostatically favorable and unfavorable interactions, respectively. These results suggest that hCT fibrils are formed by stacking antiparallel beta-sheets at pH 7.5 and a mixture of antiparallel and parallel beta-sheets at pH 3.3. This model is hosted on BioModels Database and identified by: BIOMD0000000614. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Thawfeek Varusai

PROVIDER: BIOMD0000000614 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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Conformational transitions and fibrillation mechanism of human calcitonin as studied by high-resolution solid-state 13C NMR.

Kamihira M M Naito A A Tuzi S S Nosaka A Y AY Saitô H H

Protein science : a publication of the Protein Society 20000501 5

Conformational transitions of human calcitonin (hCT) during fibril formation in the acidic and neutral conditions were investigated by high-resolution solid-state 13C NMR spectroscopy. In aqueous acetic acid solution (pH 3.3), a local alpha-helical form is present around Gly10 whereas a random coil form is dominant as viewed from Phe22, Ala26, and Ala31 in the monomer form on the basis of the 13C chemical shifts. On the other hand, a local beta-sheet form as viewed from Gly10 and Phe22, and both ...[more]

PMID: 10850796

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