Related ArticlesSolution NMR structure and inhibitory effect against amyloid-? fibrillation of Humanin containing a D-isomerized serine residue.
Biochem Biophys Res Commun. 2016 Jun 24;
Authors: Alsanousi N, Sugiki T, Furuita K, So M, Lee YH, Fujiwara T, Kojima C
Abstract
Humanin comprising 24 amino acid residues is a bioactive peptide that has been isolated from the brain tissue of patients with Alzheimer's disease. Humanin reportedly suppressed aging-related death of various cells due to amyloid fibrils and oxidative stress. There are reports that the cytoprotective activity of Humanin was remarkably enhanced by optical isomerization of the Ser14 residue from L to D form, but details of the molecular mechanism remained unclear. Here we demonstrated that Humanin D-Ser14 exhibited potent inhibitory activity against fibrillation of amyloid-? and remarkably higher binding affinity for amyloid-? than that of the Humanin wild-type and S14G mutant. In addition, we determined the solution structure of Humanin D-Ser14 by nuclear magnetic resonance (NMR) and showed that D-isomerization of the Ser14 residue enables drastic conformational rearrangement of Humanin. Furthermore, we identified an amyloid-?-binding site on Humanin D-Ser14*at atomic resolution by NMR. These biophysical and high-resolution structural analyses clearly revealed structure-function relationships of Humanin and explained the driving force of the drastic conformational change and molecular basis of the potent anti-amyloid-? fibrillation activity of Humanin caused by D-isomerization of the Ser14 residue. This is the first study to show correlations between the functional activity, tertiary structure, and partner recognition mode of Humanin and may lead to elucidation of the molecular mechanisms of the cytoprotective activity of Humanin.
PMID: 27349871 [PubMed - as supplied by publisher]
[NMR paper] Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field.
Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field.
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J Chem Theory Comput. 2015 Mar 10;11(3):1315-1329
Authors: Li S, Andrews CT, Frembgen-Kesner T, Miller MS, Siemonsma SL, Collingsworth TD, Rockafellow IT, Ngo NA,...
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[NMR paper] Potent ?-secretase inhibitors/modulators interact with Amyloid-? fibrils but do not inhibit fibrillation: A high-resolution NMR study.
Potent ?-secretase inhibitors/modulators interact with Amyloid-? fibrils but do not inhibit fibrillation: A high-resolution NMR study.
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Biochem Biophys Res Commun. 2014 Apr 16;
Authors: Yesuvadian R, Krishnamoorthy J, Ramamoorthy A, Bhunia A
Abstract
Recently, ?-secretase modulators (GSM) have been shown to interact directly with the amyloid precursor protein (APP) and...
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04-22-2014 03:54 PM
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ?-protein fibrils.
Bioorg Med Chem. 2011 Aug 27;
Authors: Masuda Y, Fukuchi M, Yatagawa T, Tada M, Takeda K, Irie K, Akagi KI, Monobe Y, Imazawa T, Takegoshi K
Abstract
Aggregation of 42-residue amyloid ?-protein (A?42) plays a pivotal role in the etiology of Alzheimer's disease (AD). Curcumin, the yellow pigment in the rhizome of turmeric, attracts...
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09-20-2011 03:10 PM
Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer’s ? by Solid-State NMR Spectroscopy
Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer’s ? by Solid-State NMR Spectroscopy
Sudhakar Parthasarathy, Fei Long, Yifat Miller, Yiling Xiao, Dan McElheny, Kent Thurber, Buyong Ma, Ruth Nussinov and Yoshitaka Ishii
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja1072178/aop/images/medium/ja-2010-072178_0006.gif
Journal of the American Chemical Society
DOI: 10.1021/ja1072178
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA ...
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[NMR paper] Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's
Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's beta-amyloid peptide, and structural characterization by solid state NMR.
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Biochemistry. 2000 Nov 14;39(45):13748-59
Authors: Balbach JJ, Ishii Y, Antzutkin ON, Leapman RD, Rizzo NW, Dyda F, Reed J, Tycko R
The seven-residue peptide N-acetyl-Lys-Leu-Val-Phe-Phe-Ala-Glu-NH(2), called A...
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[NMR paper] NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein
NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_120x27.gif Related Articles NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
J Neurochem. 1994 Jan;62(1):349-54
Authors: Klunk WE, Xu CJ, Pettegrew JW
The beta/A4-amyloid protein (beta/A4) and many synthetic fragments of this protein have proved to be very difficult to solubilize, leading to...
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[NMR paper] NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein
NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_120x27.gif Related Articles NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
J Neurochem. 1994 Jan;62(1):349-54
Authors: Klunk WE, Xu CJ, Pettegrew JW
The beta/A4-amyloid protein (beta/A4) and many synthetic fragments of this protein have proved to be very difficult to solubilize, leading to...
Solution NMR structure and inhibitory effect against amyloid-? fibrillation of Humanin containing a D-isomerized serine residue.
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