16 research outputs found
Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif
Background
There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology
A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results
The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins\u27 interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions
Exposure of consumers to substandard antibiotics from selected authorised and unauthorised medicine sales outlets in Ghana
Responsiveness and adaptability in community engaged biobanking research: experiences from a Hispanic community
Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis
CB1 cannabinoid receptor-mediated plasticity of GABAergic synapses in the mouse insular cortex
Cannabis Use Disrupts Eyeblink Conditioning: Evidence for Cannabinoid Modulation of Cerebellar-Dependent Learning
People living with HIV and the emerging field of chronic pain—what is known about epidemiology, etiology, and management
The probability of neurotransmitter release: variability and feedback control at single synapses
Information transfer at chemical synapses occurs when vesicles fuse with the plasma membrane and release neurotransmitter. This process is stochastic and its likelihood of occurrence is a crucial factor in the regulation of signal propagation in neuronal networks. The reliability of neurotransmitter release can be highly variable: experimental data from electrophysiological, molecular and imaging studies have demonstrated that synaptic terminals can individually set their neurotransmitter release probability dynamically through local feedback regulation. This local tuning of transmission has important implications for current models of single-neuron computation