A numerical investigation into possible mechanisms by that the A629P mutant of ATP7A causes Menkes Disease.
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.
Kouza
Maksim
M
Department of Physics, Michigan Technological University, Houghton, MI 49931, USA. mkouza@mtu.edu
Gowtham
S
S
Seel
Max
M
Hansmann
Ulrich H E
UH
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017433:Protein Structure, Secondary
D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases