Human Menkes X-chromosome disease and the staphylococcal cadmium-resistance ATPase: a remarkable similarity in protein sequences.
A search with the proposed amino acid translation product from the new 'candidate gene' for human Menkes disease against protein sequence libraries showed a remarkable similarity to that for the cadmium efflux ATPase from Staphylococcus aureus resistance plasmids. The Menkes sequence appears closer to the CadA Cd2+ sequence than to P-type ATPases from animal sources. Menkes syndrome is an X-chromosome invariably fatal disease that results from aberrant copper metabolism. The gene that is defective in Menkes patients, i.e. the Menkes candidate gene, encodes a P-type ATPase, whose properties satisfactorily explain the phenotype of the disease. P-type ATPases are all cation pumps, either for uptake (e.g. the bacterial Kdp K+ ATPase), for efflux (e.g. the muscle sarcoplasmic reticulum Ca2+ ATPase), or for cation exchange (e.g. the animal cell Na+/K+ ATPase). These enzymes have a conserved aspartate residue that is transiently phosphorylated from ATP during the transport cycle, hence the name 'P-type' ATPase. The Menkes sequence shares with the staphylococcal CadA ATPase those regions common to all P-type ATPases and also an N-terminal dithiol region that was proposed to be a 'metal-binding motif'. There are one or two copies of this motif in the available CadA sequences and six copies in the Menkes sequence.
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Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
Nucifora
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Phung
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D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D001693:Biological Transport, Active / Q000235:genetics; D002104:Cadmium / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism; D004352:Drug Resistance, Microbial; D005796:Genes; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011815:R Factors / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics
D001426:Bacterial Proteins; D002412:Cations; D002104:Cadmium; D000251:Adenosine Triphosphatases; C059771:cadmium translocating ATPase