Topic
ATPase binding
About: ATPase binding is a research topic. Over the lifetime, 33 publications have been published within this topic receiving 887 citations.
Papers
TL;DR: The proposed activity of R207910 against Mycobacterium tuberculosis is based on interference of the compound with the escapement geometry of the proton transfer chain, corroborated by the good agreement between the computed interaction energies and the observed pattern of stereo‐specificity in the model of the binding region.
Abstract: Diarylquinolines (DARQs) are a new class of potent inhibitors of the ATPase of Mycobacterium tuberculosis. We have created a homology model of a binding site for this class of compounds located on the contact area of the a-subunit (gene atpB) and c-subunits (gene atpE) of Mycobacterium tuberculosis ATPase. The binding pocket that was identified from the analysis of the homology model is formed by 4 helices of three c-subunits and 2 helices of the a-subunit. The lead compound of the DARQ series, R207910, was docked into the pocket using a simulated annealing, multiple conformer, docking algorithm. Different stereoisomers were treated separately. The best docking pose for each stereoisomer was optimized by molecular dynamics simulation on the 5300 atoms of the binding region and ligand. The interaction energies in the computed complexes enable us to rank the different stereoisomers in order of interaction strength with the ATPase binding pockets. We propose that the activity of R207910 against Mycobacterium tuberculosis is based on interference of the compound with the escapement geometry of the proton transfer chain. Upon binding the compound mimicks the conserved Arg-186 residue of the a-subunit and interacts in its place with the conserved acidic residue Glu-61 of the c-subunit. This mode of action is corroborated by the good agreement between the computed interaction energies and the observed pattern of stereo-specificity in the model of the binding region. Proteins 2007. © 2007 Wiley-Liss, Inc.
132 citations
TL;DR: The conclusion that the ATPase comprises 50% of the sarcoplasmic reticulum vesicle protein agrees with estimates gained from densitometry using 7 1/2% Laemmli slab gels but not from densitate using 7% Weber and Osborn slab gELs.
81 citations
TL;DR: A critical enzyme in protein breakdown in Escherichia coli is the ATP-hydrolyzing protease La, the lon gene product, and ATP and ADP binding to this enzyme is studied using rapid gel filtration to separate free from bound ligands.
60 citations
TL;DR: This is the first study which investigates the ligand affinities of P-gp from three different species and provides an example of how to use membrane P-GP ATPase assays to evaluate interspecies P- gp differences.
Abstract: P-glycoprotein (P-gp) is a transmembrane efflux transporter which possesses many important functions in drug absorption, disposition, metabolism, and toxicity. The ultimate goal of investigating drug interactions between P-gp and drug molecules in early drug discovery is to understand the contribution of P-gp to the pharmacokinetic and pharmacodynamic properties of drug candidates and to project drug-drug interaction (DDI) potentials in humans. Understanding species differences in P-gp activities further helps the prediction of P-gp-mediated drug disposition and DDI in humans from preclinical pharmacokinetics data. The objective of the present study is to investigate the species difference in P-gp activities, via P-gp ATPase assays, using rhesus monkey Mdr1, beagle dog Mdr1, and human MDR1 expressed insect cell membranes. Twenty-one compounds with diverse chemical structures and different P-gp binding sites were chosen for the ATPase assays. P-gp ATPase binding affinities (alphaKa) and fold increases in P-gp ATPase activities (beta) of P-gp substrates were determined. Consistent with the gene and amino acid similarity, the binding affinities of test compounds to rhesus monkey P-gp were much closer to those of human P-gp than beagle dog P-gp. This is the first study which investigates the ligand affinities of P-gp from three different species. The result of this study provides an example of how to use membrane P-gp ATPase assays to evaluate interspecies P-gp differences.
55 citations
TL;DR: Recent biochemical and structural studies relevant to the mechanism of ATP-dependent processive proteolysis indicate that the nucleotide occupancy of the ATPase binding sites can influence the binding mode and/or binding affinity for protein substrates.
Abstract: Clp, Lon, and FtsH proteases are proteolytic molecular machines that use the free energy of ATP hydrolysis to unfold protein substrates and processively present them to protease active sites. Here we review recent biochemical and structural studies relevant to the mechanism of ATP-dependent processive proteolysis. Despite the significant structural differences among the Clp, Lon, and FtsH proteases, these enzymes share important mechanistic features. In these systems, mechanistic studies have provided evidence for ATP binding and hydrolysis-driven conformational changes that drive translocation of substrates, which has significant implications for the processive mechanism of proteolysis. These studies indicate that the nucleotide (ATP, ADP, or nonhydrolyzable ATP analogues) occupancy of the ATPase binding sites can influence the binding mode and/or binding affinity for protein substrates. A general mechanism is proposed in which the communication between ATPase active sites and protein substrate binding regions coordinates a processive cycle of substrate binding, translocation, proteolysis, and product release.
43 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2020 | 2 |
| 2018 | 2 |
| 2014 | 1 |
| 2008 | 1 |
| 2007 | 1 |
| 2006 | 1 |