1yjt
From Proteopedia
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| Ligands: | |||||||
| Gene: | ATP7A (Homo sapiens) | ||||||
| Activity: | Copper-exporting ATPase, with EC number 3.6.3.4 | ||||||
| Related: | 1YJR, 1YJU, 1YJV
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 disease associated with this structure: Cutis laxa, neonatal OMIM:[300011], Menkes disease OMIM:[300011], Occipital horn syndrome OMIM:[300011]
About this Structure
1YJT is a Single protein structure of sequence from Homo sapiens. 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 Mar 31 01:10:04 2008
