PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Active-Site Environment of Copper-Bound Human Amylin Relevant to Type 2 Diabetes.

Abstract Type 2 diabetes mellitus (T2Dm) is characterized by reduced β cell mass and amyloid deposits of human islet amyloid polypeptide (hIAPP) or amylin, a 37 amino acid containing peptide around pancreatic β cells. The interaction of copper (Cu) with amylin and its mutants has been studied in detail using absorption, circular dichroism, electron paramagnetic resonance spectroscopy, and cyclic voltammetry. Cu binds amylin in a 1:1 ratio, and the binding domain lies within the first 19 amino acid residues of the peptide. Depending on the pH of the medium, Cu-amylin shows the formation of five pH-dependent components (component IV at pH 4.0, component III at pH 5.0, component II at pH 6.0, component I at pH 8.0, and another higher pH component above pH 9.0). The terminal amine, His18, and amidates are established as key residues in the peptide that coordinate the Cu center. The physiologically relevant components I and II can generate H2O2, which can possibly account for the enhanced toxicity of amylin in the presence of Cu, causing damage of the β cells of the pancreas via oxidative stress.
PMID
Related Publications

The amylin peptide implicated in type 2 diabetes stimulates copper-mediated carbonyl group and ascorbate radical formation.

Copper-mediated formation of hydrogen peroxide from the amylin peptide: a novel mechanism for degeneration of islet cells in type-2 diabetes mellitus?

New Insight in Copper-Ion Binding to Human Islet Amyloid: The Contribution of Metal-Complex Speciation To Reveal the Polypeptide Toxicity.

Copper(II)-human amylin complex protects pancreatic cells from amylin toxicity.

Copper Coordination Features of Human Islet Amyloid Polypeptide: The Type 2 Diabetes Peptide.

Authors

Mayor MeshTerms
Keywords
Journal Title inorganic chemistry
Publication Year Start




PMID- 29251925
OWN - NLM
STAT- Publisher
LR  - 20171220
IS  - 1520-510X (Electronic)
IS  - 0020-1669 (Linking)
DP  - 2017 Dec 18
TI  - Active-Site Environment of Copper-Bound Human Amylin Relevant to Type 2 Diabetes.
LID - 10.1021/acs.inorgchem.7b02266 [doi]
AB  - Type 2 diabetes mellitus (T2Dm) is characterized by reduced beta cell mass and
      amyloid deposits of human islet amyloid polypeptide (hIAPP) or amylin, a 37 amino
      acid containing peptide around pancreatic beta cells. The interaction of copper
      (Cu) with amylin and its mutants has been studied in detail using absorption,
      circular dichroism, electron paramagnetic resonance spectroscopy, and cyclic
      voltammetry. Cu binds amylin in a 1:1 ratio, and the binding domain lies within
      the first 19 amino acid residues of the peptide. Depending on the pH of the
      medium, Cu-amylin shows the formation of five pH-dependent components (component 
      IV at pH 4.0, component III at pH 5.0, component II at pH 6.0, component I at pH 
      8.0, and another higher pH component above pH 9.0). The terminal amine, His18,
      and amidates are established as key residues in the peptide that coordinate the
      Cu center. The physiologically relevant components I and II can generate H2O2,
      which can possibly account for the enhanced toxicity of amylin in the presence of
      Cu, causing damage of the beta cells of the pancreas via oxidative stress.
FAU - Seal, Manas
AU  - Seal M
AD  - Department of Inorganic Chemistry, Indian Association for the Cultivation of
      Science , Jadavpur, Kolkata 700032, India.
FAU - Dey, Somdatta Ghosh
AU  - Dey SG
AUID- ORCID: http://orcid.org/0000-0002-6142-2202
AD  - Department of Inorganic Chemistry, Indian Association for the Cultivation of
      Science , Jadavpur, Kolkata 700032, India.
LA  - eng
PT  - Journal Article
DEP - 20171218
PL  - United States
TA  - Inorg Chem
JT  - Inorganic chemistry
JID - 0366543
EDAT- 2017/12/19 06:00
MHDA- 2017/12/19 06:00
CRDT- 2017/12/19 06:00
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
PHST- 2017/12/19 06:00 [entrez]
AID - 10.1021/acs.inorgchem.7b02266 [doi]
PST - aheadofprint
SO  - Inorg Chem. 2017 Dec 18. doi: 10.1021/acs.inorgchem.7b02266.