Looking for the Origin of Allosteric Cooperativity in Metallopolymers.

Chemistry

Department of Inorganic, Analytical and Applied Chemistry, University of Geneva, 30 quai E. Ansermet, 1211, Geneva 4, Switzerland.

Published: June 2016

The basic concept of allosteric cooperativity used in biology, chemistry and physics states that any change in the intermolecular host-guest interactions operating in multisite receptors can be assigned to intersite interactions. Using lanthanide metals as guests and linear multi-tridentate linear oligomers of variable lengths and geometries as hosts, this work shows that the quantitative modeling of metal loadings requires the consideration of a novel phenomenon originating from solvation processes. It stepwise modulates the intrinsic affinity of each isolated site in multisite receptors, and this without resorting to allosteric cooperativity. An easy-to-handle additive model predicts a negative power law dependence of the intrinsic affinity on the length of the linear metallopolymer. Applied to lanthanidopolymers, the latter common analysis overestimates cooperativity factors by more than two orders of magnitude.

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.201600857DOI Listing

Publication Analysis

Top Keywords

allosteric cooperativity
12
multisite receptors
8
intrinsic affinity
8
origin allosteric
4
cooperativity
4
cooperativity metallopolymers
4
metallopolymers basic
4
basic concept
4
concept allosteric
4
cooperativity biology
4

Similar Publications

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

View Article and Find Full Text PDF

CRISPR-Cas12a is widely used for genome editing and biomarker detection since it can create targeted double-stranded DNA breaks and promote non-specific DNA cleavage after identifying specific DNA. To mitigate the off-target DNA cleavage of Cas12a, we previously developed a Cas12a variant (FnoCas12a ) by introducing double proline substitutions (K969P/D970P) in a conserved helix called the bridge helix (BH). In this work, we used cryogenic electron microscopy (cryoEM) to understand the molecular mechanisms of BH- mediated activation of Cas12a.

View Article and Find Full Text PDF

Regulation of enzymatic lipid peroxidation in osteoblasts protects against postmenopausal osteoporosis.

Nat Commun

January 2025

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China.

Oxidative stress plays a critical role in postmenopausal osteoporosis, yet its impact on osteoblasts remains underexplored, limiting therapeutic advances. Our study identifies phospholipid peroxidation in osteoblasts as a key feature of postmenopausal osteoporosis. Estrogen regulates the transcription of glutathione peroxidase 4 (GPX4), an enzyme crucial for reducing phospholipid peroxides in osteoblasts.

View Article and Find Full Text PDF

The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.

View Article and Find Full Text PDF

CDK2 plays a pivotal role in controlling the cell cycle progression in eukaryotes and for this reason, it has been the subject of several studies for suitable inhibitors in the last decades. But more than 30 years of basic research have not generated an inhibitor as marketed drugs. Some inhibitors are to date in early phase clinical development.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!