☆ 4.4 Review

Multiple conformational selection and induced fit events take place in allosteric propagation

BIOPHYSICAL CHEMISTRY (2014)

获取全文
添加到收藏夹

期刊

BIOPHYSICAL CHEMISTRY
卷 186, 期 -, 页码 22-30

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bpc.2013.10.002

关键词

Conformational selection; Induced fit; Allostery; Allosteric; Binding; Molecular recognition

类别

Biochemistry & Molecular Biology Biophysics Chemistry, Physical

资金

  1. National Cancer Institute
  2. National Institutes of Health [HHSN261200800001E]
  3. Intramural Research Program of the NIH
  4. Center for Cancer Research

向作者/读者索取更多资源

Protocol

社区支持

Reagent

社区支持

The fact that we observe a single conformational selection event during binding does not necessarily mean that only a single conformational selection event takes place, even though this is the common assumption. Here we suggest that conformational selection takes place not once in a given binding/allosteric event, but at every step along the allosteric pathway. This view generalizes conformational selection and makes it applicable also to other allosteric events, such as post-translational modifications (PTMs) and photon absorption. Similar to binding, at each step along a propagation pathway, conformational selection is coupled with induced fit which optimizes the interactions. Thus, as in binding, the allosteric effects induced by PTMs and light relate not only to population shift; but to conformational selection as well. Conformational selection and population shift take place conjointly. (c) 2013 Elsevier B.V. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Review Biochemistry & Molecular Biology

Allostery, and how to define and measure signal transduction

Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang

Summary: This article discusses the concept of productive signaling, including its definition, measurement, and determining factors. It highlights the importance of understanding signal propagation in diseases like cancer and neurodevelopmental disorders. The authors propose a framework for investigating signal transduction by defining cellular processes, conducting experimental measurements, and utilizing computational AI algorithms.

BIOPHYSICAL CHEMISTRY (2022)

添加到收藏夹
Article Biophysics

The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia

Yonglan Liu, Hyunbum Jang, Mingzhen Zhang, Chung-Jung Tsai, Ryan Maloney, Ruth Nussinov

Summary: This study provides insights into the molecular mechanism of BCR-ABL recruitment of GRB2, revealing the determinants of specificity in the recognition between SH2(GRB2) and phosphorylated BCR. The findings contribute to the prediction of BCR-binding scaffolds and the design of therapeutic peptides.

BIOPHYSICAL JOURNAL (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

The mechanism of activation of MEK1 by B-Raf and KSR1

Ryan C. Maloney, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov

Summary: Interactions between MEK1, B-Raf, and KSR1 are crucial for Ras/Raf/MEK/ERK signaling. Molecular dynamics simulations reveal that the proline-rich loop of MEK1 is essential for the phosphorylation of MEK1 activation loop. In the inactive B-Raf/MEK1 complex, the collapsed A-loop of B-Raf interacts with the P-rich loop and A-loop of MEK1, preventing phosphorylation. In the active B-Raf/MEK1 complex, the P-rich loop moves with the extended A-loop of B-Raf, leading to increased A-loop fluctuation and phosphorylation. KSR1/MEK1 complex has fewer interactions between KSR1 alpha G-helix and MEK1 A-loop, resulting in a more flexible A-loop.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

Artificial intelligence approaches to human-microbiome protein-protein interactions

Hansaim Lim, Fatma Cankara, Chung -Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy

Summary: This review discusses recent advancements in computational methods for predicting microbial effects on human cells, with a focus on protein-protein interactions. Traditional methods, as well as more recent deep learning methods, are categorized and potential solutions to challenges in structure-based approaches are discussed. The review provides a brief guide to the current status and future directions in the field.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2022)

添加到收藏夹
Review Biochemistry & Molecular Biology

Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs

Ruth Nussinov, Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Chung -Jung Tsai, Hyunbum Jang

Summary: This article discusses the principles and applications of allosteric activating mutations and drugs, using examples from the Ras signaling network. Specifically, it focuses on Abl kinase mutations that shift the conformation towards an active state, leading to competition between high affinity ATP and drug binding. Recent pharmacological innovation includes allosteric inhibitors and allosteric heterobifunctional degraders that can destroy targets. The design of chemical linkers in bifunctional degraders allows precise coordination between the target protein and the E3 ubiquitin ligase, enabling innovative drug discovery.

JOURNAL OF MOLECULAR BIOLOGY (2022)

添加到收藏夹
Review Multidisciplinary Sciences

Neurodevelopmental disorders, immunity, and cancer are connected

Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang

Summary: Immunity plays a crucial role in both neurodevelopmental disorders and cancer, as the immune and nervous systems coevolve during embryonic development. Dysregulated signaling caused by germline or embryonic mutations can lead to changes in chromatin organization and gene accessibility, affecting the expression of essential genes in neurodevelopment. Similarly, dysregulated signaling resulting from somatic mutations contributes to cancer development. Both conditions involve small GTPases and their pathways, as well as dysregulation of TLRs, IL-1, GIT1, and FGFR signaling pathways. However, key differentiating factors are the timing and level of perturbation in specific cell types, indicating chromatin reorganization.

ISCIENCE (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire

Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov

Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.

PROTEIN SCIENCE (2023)

添加到收藏夹
Letter Oncology

Activation mechanisms of clinically distinct B-Raf V600E and V600K mutants

Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Hyunbum Jang, Ruth Nussinov

CANCER COMMUNICATIONS (2023)

添加到收藏夹
Review Pharmacology & Pharmacy

AlphaFold, allosteric, and orthosteric drug discovery: Ways forward

Ruth Nussinov, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang

Summary: Drug discovery is a highly challenging and significant interdisciplinary aim. The success of AlphaFold, an AI-powered technology, has raised hopes for drug discovery, but its limitations need to be considered. Improving AlphaFold's performance in active state models can enhance the success rate of rational drug design.

DRUG DISCOVERY TODAY (2023)

添加到收藏夹
Article Chemistry, Physical

Strategy toward Kinase-Selective Drug Discovery

Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov

Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2023)

添加到收藏夹
Review Biophysics

Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK

Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Mingzhen Zhang, Yonglan Liu, Chung-Jung Tsai, Hyunbum Jang, Nurcan Tuncbag

Summary: Neurodevelopmental disorders (NDDs) and cancer have similarities in terms of proteins, pathways, and mutations, but have different clinical symptoms. However, individuals with NDDs have a higher likelihood of developing cancer later on. This review explores how shared features can result in different medical conditions and why having an NDD first can increase the chances of malignancy.

BIOPHYSICAL REVIEWS (2023)

添加到收藏夹
Article Genetics & Heredity

Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome

Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag

Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.

NPJ GENOMIC MEDICINE (2023)

添加到收藏夹
Article Biochemistry & Molecular Biology

Cell phenotypes can be predicted from propensities of protein conformations

Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang

Summary: The propensities of protein conformations can predict cell function and suggest drug efficiency.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2023)

添加到收藏夹
Review Biochemistry & Molecular Biology

Protein conformational ensembles in function: roles and mechanisms

Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang

Summary: The sequence-structure-function paradigm in molecular biology has been updated to include the concept of conformational ensembles, recognizing that proteins are dynamic and constantly transitioning between different conformational states. The number and stability of these states are crucial for protein function. Understanding conformational propensities is essential for studying diverse systems and can provide insights into the dynamics of protein ensembles in cells.

RSC CHEMICAL BIOLOGY (2023)

添加到收藏夹
Article Genetics & Heredity

Predictive modeling of moonlighting DNA-binding proteins

Dana Mary Varghese, Ruth Nussinov, Shandar Ahmad

Summary: Moonlighting proteins are capable of performing multiple autonomous functions. In this study, human moonlighting DNA-binding proteins (mDBPs) were investigated and found to be distinguishable from other proteins with the same DNA-binding function. A machine learning model was developed to predict mDBPs from other DBPs with high accuracy.

NAR GENOMICS AND BIOINFORMATICS (2022)

添加到收藏夹
Article Biochemistry & Molecular Biology

TPE conjugated islet amyloid polypeptide probe for detection of peptide oligomers

Hsiao-Chieh Tsai, Ching-Hong Huang, Ling-Hsien Tu

Summary: Islet amyloid polypeptide (IAPP) is a polypeptide hormone co-secreted with insulin by pancreatic beta-cells. It tends to aggregate into soluble oligomers, which are considered one of the hallmarks of type II diabetes. This study successfully grafted the aggregation-induced emission molecule TPE onto IAPP, allowing real-time monitoring of IAPP oligomer formation and potential application in the diagnosis of T2D.

BIOPHYSICAL CHEMISTRY (2024)

添加到收藏夹
Article Biochemistry & Molecular Biology

Thermally stabilized chondroitin sulfate-hemoglobin nanoparticles and their interaction with bioactive compounds

Aristeidis Papagiannopoulos, Aggeliki Sklapani, Nikolaos Spiliopoulos

Summary: This study presents a method for preparing Hb-based nanoparticles (NPs) using a fully biocompatible approach. These NPs have a spherical structure with a diameter ranging from 50 to 100 nm, and can form electrostatic complexes with CS at pH 4. The NPs can be pH-tunable and stable in solutions with high salt content, making them suitable for nanodelivery of nutrients and drugs.

BIOPHYSICAL CHEMISTRY (2024)

添加到收藏夹
Article Biochemistry & Molecular Biology

Osmotic stress studies of G-protein-coupled receptor rhodopsin activation

Andrey V. Struts, Alexander V. Barmasov, Steven D. E. Fried, Kushani S. K. Hewage, Suchithranga M. D. C. Perera, Michael F. Brown

Summary: This article summarizes and reviews the osmotic stress studies of G-protein-coupled receptor rhodopsin. It is found that water plays an important role in the activation of the receptor, with at least 80 water molecules entering the receptor in the transition to the active state. If water influx is prevented, the functional transition of the receptor is reversed. These findings reveal the phenomenon of solvent swelling in the activation mechanism of rhodopsin, with water acting as an allosteric modulator of function for rhodopsin-like receptors in lipid membranes.

BIOPHYSICAL CHEMISTRY (2024)

添加到收藏夹
Article Biochemistry & Molecular Biology

Palmitoylation modifies transmembrane adaptor protein PAG for ordered lipid environment: A molecular dynamics simulation study

Maria Chiara Saija, Adela Melcrova, Wojciech Pajerski, Itay Schachter, Matti Javanainen, Marek Cebecauer, Lukasz Cwiklik

Summary: We used molecular dynamics simulations to investigate the effects of palmitoylation on a transmembrane peptide in different lipid environments. The study found that palmitoylation reduces the peptide's impact on membrane thickness, particularly in lipid-ordered and boundary environments. The hydrophobic palmitoyl chains on the peptide did not significantly affect membrane hydration. Interestingly, the boundary membrane environment was found to be highly compatible with the palmitoylated peptide. These findings have important implications for understanding cell signaling, membrane organization, and optimizing lipid membrane-based drug delivery systems.

BIOPHYSICAL CHEMISTRY (2024)

添加到收藏夹
Article Biochemistry & Molecular Biology

Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells

Achanta Rishisree, Brayer Mallory, Karnaukhova Elena, Jankovic Teodora, Zdunic Gordana, Savikin Katarina, Jeremic Aleksandar

Summary: Pomegranate peel, ironwort, and chokeberry leaf extracts exhibit anti-aggregative and antitoxic properties against human amylin. They can prevent amyloidosis and cell loss in patients with Type 2 Diabetes Mellitus.

BIOPHYSICAL CHEMISTRY (2024)

添加到收藏夹
研讨会 海报 问题 讨论圈 基金 期刊 论文 科研社交 资讯集成 审稿人 关于我们 常见问题 移动App 隐私条款 使用条款
© Peeref 2019-2024. All rights reserved.