Results 51 to 60 of about 81,932 (256)

Bias-inducing allosteric binding site in mu-opioid receptor signaling

SN Applied Sciences, 2021
G-protein-biased agonism of the mu-opioid receptor (μ-OR) is emerging as a promising strategy in analgesia. A deep understanding of how biased agonists modulate and differentiate G-protein-coupled receptors (GPCR) signaling pathways and how this is ...
Andrés F. Marmolejo-Valencia, Abraham Madariaga-Mazón, Karina Martinez-Mayorga   +2 more
doaj   +1 more source

Interpreting the effects of DNA polymerase variants at the structural level

Molecular Oncology, EarlyView.
Using MAVISp and molecular dynamics simulations, we analyzed over 60 000 missense variants in POLE and POLD1 from ClinVar, COSMIC, cBioPortal, and saturation mutagenesis. Identified mechanistic indicators, including stability, binding, and long‐range, enable structural interpretation, providing ACMG‐like evidence for possible reclassification of VUS ...
Matteo Arnaudi, Karolina Krzesińska, Ludovica Beltrame, Pablo Sánchez‐Izquierdo Besora, Matteo Tiberti, Mef Nilbert, Anna Rohlin, Elena Papaleo   +7 more
wiley   +1 more source

Surface Sites for Engineering Allosteric Control in Proteins [PDF]

Science, 2008
Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the ...
Jeeyeon, Lee, Madhusudan, Natarajan, Vishal C, Nashine, Michael, Socolich, Tina, Vo, William P, Russ, Stephen J, Benkovic, Rama, Ranganathan   +7 more
openaire   +2 more sources

Loss of proton‐sensing TDAG8 increases tumor progression in mouse models of colon cancer

Molecular Oncology, EarlyView.
Loss of the pH‐sensing receptor TDAG8 accelerates colorectal cancer progression in mice. Animals lacking TDAG8 expression had increased tumor growth, DNA damage, and recruitment of tumor‐associated immune cells, including macrophages, neutrophils, and monocytes.
Ermanno Malagola, Yasmine Illi, Anna Bircher, Marijn Wilmink, Rachele F. Malagutti, Solenn Ottié, Cordelia Schuler, Pedro A. Ruiz, Cheryl de Vallière, Klaus Seuwen, Gerhard Rogler, Martin Hausmann   +11 more
wiley   +1 more source

Analysing the significance of small conformational changes and low occupancy states in serial crystallographic data

FEBS Open Bio, EarlyView.
This protocol paper outlines methods to establish the success of a time‐resolved serial crystallographic experiment, by means of statistical analysis of timepoint data in reciprocal space and models in real space. We show how to amplify the signal from excited states to visualise structural changes in successful experiments.
Jake Hill, Yelyzaveta Pulnova, Elke De Zitter, Helen M. Ginn, Briony A. Yorke   +4 more
wiley   +1 more source

Illuminating the mechanism and allosteric behavior of NanoLuc luciferase

Nature Communications, 2023
NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel ...
Michal Nemergut, Daniel Pluskal, Jana Horackova, Tereza Sustrova, Jan Tulis, Tomas Barta, Racha Baatallah, Glwadys Gagnot, Veronika Novakova, Marika Majerova, Karolina Sedlackova, Sérgio M. Marques, Martin Toul, Jiri Damborsky, Zbynek Prokop, David Bednar, Yves L. Janin, Martin Marek   +17 more
doaj   +1 more source

Allostery Inhibition of BACE1 by Psychotic and Meroterpenoid Drugs in Alzheimer’s Disease Therapy

Molecules, 2022
In over a century since its discovery, Alzheimer’s disease (AD) has continued to be a global health concern due to its incurable nature and overwhelming increase among older people. In this paper, we give an overview of the efforts of researchers towards
Samuel C. Ugbaja, Isiaka A. Lawal, Bahijjahtu H. Abubakar, Aganze G. Mushebenge, Monsurat M. Lawal, Hezekiel M. Kumalo   +5 more
doaj   +1 more source

Mass spectrometry based identification of AMP‐O‐Tris generated by Thermococcus onnurineus Cas10

FEBS Open Bio, EarlyView.
Isolated Thermococcus onnurineus Cas10 generates the noncanonical ATP‐derived product AMP‐O‐Tris while in Tris‐containing buffer as identified via mass spectrometry, revealing relaxed nucleophile selectivity under isolated conditions. These findings suggest that multiprotein Csm complex assembly restricts Cas10 reactivity toward canonical cyclic ...
Su‐Jin Lee, Ga Seul Lee, JinHan Kim, Kwang‐Hyun Park, Seong‐Ryung Go, Jeong Hee Moon, Eui‐Jeon Woo   +6 more
wiley   +1 more source

Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response

PLOS Computational Biology, 2018
The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors. However, despite a general consensus on the key role of dynamics most of the earlier efforts on the prediction of allosteric
Wei-Ven Tee, Enrico Guarnera, Igor N. Berezovsky   +2 more
openaire   +4 more sources

Current Advances in Allosteric Modulation of Muscarinic Receptors

Biomolecules, 2020
Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter.
Jan Jakubik, Esam E. El-Fakahany
doaj   +1 more source