Silver S, Nucifora G, Phung L T
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
Mol Microbiol. 1993 Oct;10(1):7-12. doi: 10.1111/j.1365-2958.1993.tb00898.x.
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.
利用针对人类门克斯病新“候选基因”的氨基酸翻译产物在蛋白质序列文库中进行搜索，结果显示其与金黄色葡萄球菌耐药质粒中的镉外流ATP酶具有显著相似性。与动物来源的P型ATP酶相比，门克斯序列似乎与CadA Cd2+序列更为接近。门克斯综合征是一种X染色体连锁的、 invariably fatal disease，由异常的铜代谢引起。门克斯病患者中存在缺陷的基因，即门克斯候选基因，编码一种P型ATP酶，其特性能够令人满意地解释该疾病的表型。P型ATP酶均为阳离子泵，有的用于摄取（如细菌Kdp K+ ATP酶），有的用于外流（如肌肉肌浆网Ca2+ ATP酶），还有的用于阳离子交换（如动物细胞Na+/K+ ATP酶）。这些酶有一个保守的天冬氨酸残基，在转运循环中会从ATP短暂磷酸化，因此得名“P型”ATP酶。门克斯序列与葡萄球菌CadA ATP酶共享所有P型ATP酶共有的区域，还共享一个N端二硫醇区域，该区域被认为是一个“金属结合基序”。在现有的CadA序列中有一到两个这种基序拷贝，而在门克斯序列中有六个拷贝。
