1yju

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models PDB ID 1yju Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
Gene:	ATP7A (Homo sapiens)
Activity:	Copper-exporting ATPase, with EC number 3.6.3.4
Related:	1YJR, 1YJT, 1YJV
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Solution structure of the apo form of the sixth soluble domain of Menkes protein

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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

1YJU 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 01:10:16 2008