Return to search

Computational modeling of Ca2+ and Zn2+ competition in Calbindin D28k, implications for altering calcium homeostasis

Neurodegeneration in Alzheimer's disease is characterised by multiple pathologies including disrupted calcium homeostasis and elevated Zn2+ levels. Calbindin D28k (CB-D28k), which buffers Ca2+ and can bind Zn2+, was suspected to be involved in these abnormalities. The PDB structure of this EF-hand protein shows that not all hands are well formed. Docking and molecular dynamics calculations were employed to achieve the two goals in this project. The first goal was to get a better structure of CB-D28k to improve our understanding of its behavior. Calculations improved the structure protein: helix-loop-helix sequences were formed in all hands and most canonical interactions were formed in the four functional hands. The second goal was to test the Ca2+ binding capacity of Zn2+-bound CB-D28k. Analysis of calculated structures showed that the Ca2+ binding capability of Zn2+ bound protein was significantly compromised, permitting only half of the correct canonical interactions with the loop residues.

Identiferoai:union.ndltd.org:MANITOBA/oai:mspace.lib.umanitoba.ca:1993/14425
Date08 January 2013
CreatorsOmar, Sara
ContributorsGough, Kathleen (Chemistry), Albensi, Benedict (Pharmacology and Therapeutics) O'Neil, Joe (Chemistry) Schreckenbach, Georg (Chemistry)
Source SetsUniversity of Manitoba Canada
Detected LanguageEnglish

Page generated in 0.0019 seconds