Vanadate is the hallmark inhibitor of the P-type ATPase family; however, structural details of its inhibitory mechanism have remained unresolved. We have determined the crystal structure of sarcoplasmic reticulum Ca(2+)-ATPase with bound vanadate in the absence of Ca(2+). Vanadate is bound at the catalytic site as a planar VO3(-) in complex with water and Mg(2+) in a dephosphorylation transitio...

BACKGROUND Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporte...

Wilson disease is an autosomal recessive inherited disorder of hepatic copper metabolism resulting in the accumulation of copper in many organs and tissues. The defective gene is located on the long arm of chromosome 13 and codes for a transmembrane copper-transporting ATPase, ATP7B. The general incidence of the condition is 1:30,000 (1). Type 1 neurofibromatosis (NF-1) is one of the most commo...

As a relatively polar molecule, CDDP is thought to use specific plasma membrane systems for passage into cells, although entry by passive diffusion is also likely to occur. Alterations in these plasma membrane systems have been considered to be important resistance factors because one of the most consistent features of CDDP-resistant cell lines is decreased intracellular drug levels (1). Wherea...

A method for investigating electrogenic partial reactions in the pump cycle of membrane-bound P-type ATPases with electrochromic fluorescent dyes has been extended to detergent-solubilized native and purified recombinant Na,K-ATPase. As a first step, it has been shown here that the function and ion binding properties of the detergent-soluble and membrane-bound rabbit renal Na,K-ATPase are not s...

The detailed nature of N-3 binding at the multi-copper active site in native laccase is investigated through a combination of low-temperature magnetic circular dichroism (LTMCD) and absorption spectroscopies. This combination of techniques allows charge-transfer spectral features associated with N-3 binding to the paramagnetic type 2 Cu(II) to be differentiated from those associated with bindin...