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.
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
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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