[Androgen deprivation as initial and backbone therapy for prostate carcinoma cancer : A retrospective data analysis from urological practices in Germany].

Background: The aim of this study was to determine the proportion of patients with prostate cancer (PCa) who remained on primary androgen deprivation therapy (ADT) after starting treatment for castration-resistant prostate cancer (CRPC) and to describe their treatment patterns.

Materials And Methods: The study comprises a retrospective analysis of 609,308 patients in urological practices in Germany from 2011 to 2020 based on anonymized secondary data from the UROscience webserver. PCa patients were eligible for inclusion if they received ADT after a 6-month prescription-free pre-index period.

Involvement of the alpha-subunit N-terminus in the mechanism of the Na,K-ATPase.

Previous studies have shown that cytoplasmic K release and the associated E2 → E1 conformational change of the Na,K-ATPase is a major rate-determining step of the enzyme's ion pumping cycle and hence a prime site of acute regulatory intervention. From the ionic strength dependence of the enzyme's distribution between the E2 and E1 states, it has also been found that E2 is stabilized by an electrostatic attraction. Any disruption of this electrostatic attraction would, thus, have profound effects on the rate of ion pumping.

Crystal structures of Na ,K -ATPase reveal the mechanism that converts the K -bound form to Na -bound form and opens and closes the cytoplasmic gate.

Na ,K -ATPase (NKA) plays a pivotal role in establishing electrochemical gradients for Na and K across the cell membrane by alternating between the E1 (showing high affinity for Na and low affinity for K ) and E2 (low affinity to Na and high affinity to K ) forms. Presented here are two crystal structures of NKA in E1·Mg and E1·3Na states at 2.9 and 2.

Cryo-electron microscopy of Na ,K -ATPase reveals how the extracellular gate locks in the E2·2K state.

Na ,K -ATPase (NKA) is one of the most important members of the P-type ion-translocating ATPases and plays a pivotal role in establishing electrochemical gradients for Na and K across the cell membrane. Presented here is a 3.3 Å resolution structure of NKA in the E2·2K state solved by cryo-electron microscopy.

Cryoelectron microscopy of Na,K-ATPase in the two E2P states with and without cardiotonic steroids.

Cryoelectron microscopy (cryo-EM) was applied to Na+,K+-ATPase (NKA) to determine the structures of two E2P states, one (E2PATP) formed by ATP and Mg2+ in the forward reaction, and the other (E2PPi) formed by inorganic phosphate (Pi) and Mg2+ in the backward reaction, with and without ouabain or istaroxime, representatives of classical and new-generation cardiotonic steroids (CTSs). These two E2P states exhibit different biochemical properties. In particular, K+-sensitive acceleration of the dephosphorylation reaction is not observed with E2PPi, attributed to the presence of a Mg2+ ion in the transmembrane cation binding sites.