A numerical investigation into possible mechanisms by that the A629P mutant of ATP7A causes Menkes Disease

Phys Chem Chem Phys. 2010 Oct 7;12(37):11390-7. doi: 10.1039/c003568h. Epub 2010 Aug 16.

Abstract

We study in silico possible mechanisms by that the A629P mutant of ATP7A causes Menkes Disease. Our results indicate that the mutation does not have appreciable affects on the stability of copper-bound states but rather destabilizes the characteristic end-to-end β-sheet. In this way, the mutation presumably increases the probability for aggregation and/or degradation leading to decreased concentration of the monomer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism*
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism*
  • Copper / metabolism
  • Copper-Transporting ATPases
  • Humans
  • Menkes Kinky Hair Syndrome / genetics*
  • Menkes Kinky Hair Syndrome / metabolism
  • Models, Molecular
  • Mutation*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Cation Transport Proteins
  • Copper
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases