Theoretical characterization of Al(III) binding to KSPVPKSPVEEKG: Insights into the propensity of aluminum to interact with key sequences for neurofilament formation.

Journal of Inorganic Biochemistry
Rafael Grande-AztatziX Lopez

Abstract

Classical molecular dynamic simulations and density functional theory are used to unveil the interaction of aluminum with various phosphorylated derivatives of the fragment KSPVPKSPVEEKG (NF13), a major multiphosphorylation domain of human neurofilament medium (NFM). Our calculations reveal the rich coordination chemistry of the resultant structures with a clear tendency of aluminum to form multidentate structures, acting as a bridging agent between different sidechains and altering the local secondary structure around the binding site. Our evaluation of binding energies allows us to determine that phosphorylation has an increase in the affinity of these peptides towards aluminum, although the interaction is not as strong as well-known chelators of aluminum in biological systems. Finally, the presence of hydroxides in the first solvation layer has a clear damping effect on the binding affinities. Our results help in elucidating the potential structures than can be formed between this exogenous neurotoxic metal and key sequences for the formation of neurofilament tangles, which are behind of some of the most important degenerative diseases.

References

Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·V M LeeR A Lazzarini
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·V M LeeJ Q Trojanowski
Jan 1, 1988·Trends in Biochemical Sciences·T L Macdonald, R B Martin
Jan 28, 1994·Biochemical and Biophysical Research Communications·M KawaharaY Kuroda
Jun 1, 1994·Journal of Inorganic Biochemistry·C ExleyJ D Birchall
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·M HollósiG D Fasman
Jun 21, 1993·FEBS Letters·C ExleyJ D Birchall
May 16, 1997·The Journal of Biological Chemistry·J C BettsB H Anderton
Mar 18, 2000·Journal of Computer-aided Molecular Design·G Schaftenaar, J H Noordik
May 26, 2001·Journal of Inorganic Biochemistry·C Exley, O V Korchazhkina
Nov 20, 1996·Inorganic Chemistry·Károly AtkáriR. Bruce Martin
Jan 23, 2003·Protein Science : a Publication of the Protein Society·Michelle Scalley-KimDavid Baker
Sep 26, 2003·Journal of Inorganic Biochemistry·Christopher Exley
Nov 20, 2003·Cellular and Molecular Life Sciences : CMLS·S-J YangS-W Cho
Mar 24, 2004·Free Radical Biology & Medicine·Christopher Exley
Jul 1, 1995·Archives of Gerontology and Geriatrics·T Kiss
Jan 25, 2005·Cellular and Molecular Life Sciences : CMLS·Veer Bala GuptaK S Jagannatha Rao
Aug 12, 2005·Chemical Reviews·Jacopo TomasiRoberto Cammi
Aug 15, 2006·Journal of Biochemical and Molecular Toxicology·Ryan J MaillouxVasu D Appanna
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Aug 23, 2007·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Elixabete RezabalJesus M Ugalde
Jun 25, 2008·Annual Review of Biophysics·Todor Dudev, Carmay Lim
Jul 2, 2009·Archives of Toxicology·Vijay Kumar, Kiran Dip Gill
Sep 24, 2009·Trends in Biochemical Sciences·Christopher Exley
Mar 25, 2010·The Journal of Chemical Physics·Tatiana M C FaroMunir S Skaf
Dec 16, 2010·Journal of Alzheimer's Disease : JAD·Lucija Tomljenovic
Mar 30, 2011·Physical Chemistry Chemical Physics : PCCP·Jorge Alí-TorresMariona Sodupe
May 25, 2011·The Journal of Physical Chemistry. a·J I MujikaX Lopez
May 30, 2014·Accounts of Chemical Research·Peter FallerGiovanni La Penna
May 31, 2014·The Journal of Physical Chemistry. B·J I MujikaX Lopez
Aug 19, 2014·Physical Chemistry Chemical Physics : PCCP·Noelia B LuqueXabier Lopez
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl
May 1, 2007·Journal of Chemical Theory and Computation·Antonio Luiz Oliveira de NoronhaHélio Anderson Duarte
Feb 19, 2016·Physical Chemistry Chemical Physics : PCCP·Rafael Grande-AztatziXabier Lopez
Jan 4, 2017·Chemical Reviews·Pengfei Li, Kenneth M Merz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.