1yjt
From Proteopedia
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Solution structure of the Cu(I) form of the sixth soluble domain A69P mutant of Menkes protein
Contents |
Overview
Menkes disease is a fatal disease that can be induced by various mutations, in the ATP7A gene, leading to unpaired uptake of dietary copper. The ATP7A, gene encodes a copper(I)-translocating ATPase. Here the disease-causing, A629P mutation, which occurs in the last of the six copper(I)-binding, soluble domains of the ATPase (hereafter MNK6), was investigated. To, understand why this apparently minor amino acid replacement is pathogenic, the solution structures and dynamics on various time-scales of wild-type, and A629P-MNK6 were determined both in the apo- and copper(I)-loaded, forms. The interaction in vitro with the physiological ATP7A, copper(I)-donor (HAH1) was additionally studied. The A629P mutation makes, the protein beta-sheet more solvent accessible, possibly resulting in an, enhanced susceptibility of ATP7A to proteolytic cleavage and/or in reduced, capability of copper(I)-translocation. A small reduction of the affinity, for copper(I) is also observed. Both effects could concur to, pathogenicity.
Disease
Known diseases associated with this structure: Analgesia from kappa-opioid receptor agonist, female-specific OMIM:[155555], Blond/light brown hair and/or fair skin OMIM:[155555], Cutis laxa, neonatal OMIM:[300011], Melanoma, susceptiblity to OMIM:[155555], Menkes disease OMIM:[300011], Occipital horn syndrome OMIM:[300011], Oculocutaneous albinism, type II, modifier of OMIM:[155555], Red hair/fair skin OMIM:[155555], UV-induced skin damage, susceptibility to OMIM:[155555]
About this Structure
1YJT is a Single protein structure of sequence from Homo sapiens with CU1 as ligand. Active as Copper-exporting ATPase, with EC number 3.6.3.4 Full crystallographic information is available from OCA.
Reference
An atomic-level investigation of the disease-causing A629P mutant of the Menkes protein, ATP7A., Banci L, Bertini I, Cantini F, Migliardi M, Rosato A, Wang S, J Mol Biol. 2005 Sep 16;352(2):409-17. PMID:16083905
Page seeded by OCA on Mon Nov 12 20:20:54 2007
