PMID: 11917147Mar 28, 2002Paper

A molecular dynamics study of an L-type calcium channel model

Protein Engineering
Gabriela BarreiroRicardo Bicca de Alencastro

Abstract

In this work, we propose a molecular model of the L-type calcium channel pore from the human cardiac alpha1 subunit. Four glutamic acid residues, the EEEE locus, located at highly conserved P loops (also called SS1-SS2 segments) of the alpha1 subunit, molecularly express the calcium channel selectivity. The proposed alpha-helix structure for the SS1 segment, analyzed through molecular dynamics simulations in aqueous-phase, was validated by the plotting of Ramachandran diagrams for the averaged structures and by the analysis of i and i + 4 helical hydrogen bonding between the amino acid residues. The results of the simulation of the calcium channel model with one and two Ca2+ ions at the binding site are in accordance with mutation studies which suggest that the EEEE locus in the L-type calcium channel must form a single high-affinity binding site. These results suggest that the Ca2+ permeation through the channel would be derived from competition between two ions for the only high-affinity binding site. Furthermore, the experimentally observed blocking of the Na+ flux at micromolar Ca2+ concentrations, probably due to the occupancy of the single high-affinity binding site for one Ca2+, was also reproduced by our model.

References

May 6, 1984·Nature·P Hess, R W Tsien
Jun 28, 1993·FEBS Letters·K Imoto
Feb 1, 1995·Trends in Pharmacological Sciences·G VaradiA Schwartz
Dec 1, 1995·Journal of Molecular Graphics·S W DoughtyW G Richards
Oct 3, 1998·Journal of Bioenergetics and Biomembranes·E Perez-Reyes
Jun 3, 1999·The Journal of General Physiology·E W McCleskey
Sep 3, 1999·Critical Reviews in Biochemistry and Molecular Biology·G VaradiG Palyi
Dec 10, 1999·Molecular and Cellular Neurosciences·A Randall, C D Benham
Apr 13, 2000·The European Journal of Neuroscience·M HobomN Klugbauer
Nov 14, 2000·The Journal of Biological Chemistry·J E McRoryT P Snutch
Dec 1, 1993·The Biological Bulletin·J A Schetz, Pav Anderson

❮ Previous
Next ❯

Citations

Apr 19, 2003·Protein Engineering·Gabriela BarreiroRicardo Bicca de Alencastro
Dec 10, 2002·Annual Review of Physiology·William A Sather, Edwin W McCleskey
Aug 26, 2014·The Journal of Chemical Physics·Jinn-Liang Liu, Bob Eisenberg
Dec 17, 2014·The Journal of Chemical Physics·Jinn-Liang Liu, Bob Eisenberg
Oct 13, 2009·Biochimica Et Biophysica Acta·Attila MalasicsDezso Boda
May 18, 2004·British Journal of Anaesthesia·M Zaugg, M C Schaub
Jan 26, 2011·Physical Biology·Janhavi GiriBob Eisenberg

❮ 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.