The Structural Basis of ATP as an Allosteric Modulator

Abstract

The synaptic vesicle protein Synaptotagmin I is the calcium ion sensor for neurotransmitter release. Synaptotagmins are comprised of C2 domains, calcium ion dependent, membrane-binding domains. They contain multiple C2

Structures of a P4-ATPase lipid flippase in lipid bilayers

“…S7) (Hiraizumi et al 2019). The extended conformation suggests the structure may represent a distinct active E1-ATP state not observed before (Lu et al 2014). As a result, the N domain rotates by 35°compared to its orientation in the E2P structure ( Fig.…”

PI3K inhibitors: review and new strategies

“…However, current inhibitors are still stymied by insufficient selectivity, the outcome of the near identity among the ATP binding sites of the PI3K isoforms. At the same time, since ATP is the principal energy currency of the cell with structurally similar cavities hosting it, 26 attempts to overcome these hurdles by higher ATP-competitive drug levels encounter toxicity. This argues for allosteric drugs.…”

Raf-1 Cysteine-Rich Domain Increases the Affinity of K-Ras/Raf at the Membrane, Promoting MAPK Signaling

“…We performed the MD simulations using the AMBER 11 package (Case et al, 2005) with the AMBER ff03 force field (Damjanovi c et al, 2009). Simulations were carried out following our previously published protocols (Lu et al, 2015(Lu et al, , 2014(Lu et al, , 2016b. For all systems, the initial configurations were subjected to 2000 steps of the steepest descent energy minimization, followed by 3000 steps of the conjugate gradient energy minimization with a positional restraint of 500 kcal/mol/Å 2 imposed on the heavy atoms of the proteins, ensuring that bad contacts in the solvated systems are removed.…”