Results 61 to 70 of about 22,949 (304)

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia

Nature Communications, 2023
TRPV1 as a drug target suffers from side effects of hypothermia. Here, authors engineer a peptide, sRhTx, as a positive allosteric modulator of TRPV1 channel. It potentiates the activity of TRPV1 to reversibly ablate pain-sensing nerve terminals for long-
Heng Zhang, Jia-Jia Lin, Ya-Kai Xie, Xiu-Zu Song, Jia-Yi Sun, Bei-Lei Zhang, Yun-Kun Qi, Zhen-Zhong Xu, Fan Yang   +8 more
doaj   +1 more source

Structure-Activity Relationship Study of the High-Affinity Neuropeptide Y4 Receptor Positive Allosteric Modulator VU0506013

, 2023
Structure-Activity Relationship Study of the High-Affinity Neuropeptide Y4 Receptor Positive Allosteric Modulator ...
Y Du (6951416), HM Cox (14474847), CD Weaver (16651125), J Meiler (13321746), J Stichel (13321740), AG Beck-Sickinger (14474886), NM Mishra (7807733), IR Tough (14474838), C Schüß (13321830), O Vu (16651122), KA Emmitte (16651128)   +10 more
core  

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

Concentration dependence of the interaction of two allosteric modulators that compete for the same allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence of two allosteric modulators A and B competing for the same allosteric site, where α is either less than one (left) or greater than one (right) and B is negative allosteric modulator ...
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Molecular dynamics simulations of positively selected codons in FcγRI reveal novel biochemical binding properties

FEBS Open Bio, EarlyView.
Evolutionary analysis across 32 placental mammals identified positive selection at residues H148 and W149 in the immune receptor FcγR1. Ancestral reconstruction combined with molecular dynamics simulations reveals how these mutations may influence receptor structure and dynamics, providing insight into the evolution of antibody recognition and immune ...
David A. Young, Omar Arias‐Gaguancela, Fiona Gibson, Morgan Grainger, Jodie Score, Amit Nathubhai, Mauricio Cafiero, Lee Richard Machado   +7 more
wiley   +1 more source

Positive or negative allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) does not alter expression of behavioral sensitization to methamphetamine [v1; ref status: indexed, http://f1000r.es/o0]

F1000Research, 2013
We investigated the role of metabotropic glutamate receptor type 5 (mGluR5) in methamphetamine-induced behavioral sensitization. The mGluR5 positive allosteric modulator (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and negative allosteric ...
Peter R Kufahl, Natali E Nemirovsky, Lucas R Watterson, Nicholas Zautra, M Foster Olive   +4 more
doaj   +1 more source

Discovery of a Potent Allosteric Kinase Modulator by Combining Computational and Synthetic Methods [PDF]

, 2015
The rational design of allosteric kinase modulators is challenging but rewarding. The protein kinase PDK1, which lies at the center of the growth-factor signaling pathway, possesses an allosteric regulatory site previously validated both in vitro and in ...
Süß, Evelyn, Domling, A., Camacho, Carlos J, Evelyn Süß, Dömling, Alexander, Biondi, R.M., Alexander Dömling, Schulze, Jörg O, Jörg O. Schulze, Camacho, C.J., Kroon, Edwin, Schulze, J.O., Biondi, Ricardo M, Suess, E., Carlos J. Camacho, Kroon, E., Ricardo M. Biondi, Edwin Kroon   +17 more
core   +1 more source

Mutant NPM1 in Acute Myeloid Leukemia Initiation and Maintenance

Aging and Cancer, EarlyView.
NPM1 mutations drive acute myeloid leukemia by acting as neomorphic transcriptional regulators that cooperate with Menin–MLL and XPO1 to sustain HOX/MEIS1 expression and block differentiation. Targeting these mutant‐specific transcriptional dependencies provides a rational therapeutic strategy for NPM1‐mutated AML.
Yanan Jiang, Zhong Fan, Runmeng Liu, Xiaotian Zhang   +3 more
wiley   +1 more source

A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury

, 2018
•A PDE4D negative allosteric modulator did not alter cognition in non-injured rats.•Cognition after TBI is improved with a PDE4D negative allosteric modulator.•A PDE4D negative allosteric modulator improves LTP in TBI animals. Traumatic brain injury (TBI)
W. Dalton Dietrich, Dale A. Calixte, Gurney, Mark E, Dietrich, W. Dalton, Atkins, Coleen M, Coleen M. Atkins, Titus, David J, Wilson, Nicole M, David J. Titus, Oscar Alcazar, Alcazar, Oscar, Nicole M. Wilson, Calixte, Dale A, Mark E. Gurney   +13 more
core   +1 more source