Review
Biochemistry & Molecular Biology
Jordan Fauser, Nicholas Leschinsky, Barbara N. Szynal, Andrei V. Karginov
Summary: This review discusses recent advancements in engineered allosteric regulation, highlighting the benefits and pitfalls of various bioengineered techniques and their potential applications.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Duan Ni, Yaqin Liu, Ren Kong, Zhengtian Yu, Shaoyong Lu, Jian Zhang
Summary: This review comprehensively reviews bioinformatic methods for elucidating allosteric communication and discusses their successful applications in allosteric drug design. Current challenges and future perspectives are also discussed.
DRUG DISCOVERY TODAY
(2022)
Article
Biology
Lukasz Nierzwicki, Kyle W. East, Uriel N. Morzan, Pablo R. Arantes, Victor S. Batista, George P. Lisi, Giulia Palermo
Summary: This study combines multiple techniques to reveal the impact of key mutations for enhancing Cas9 specificity on its allosteric structure at the molecular level, demonstrating that mutations can disrupt the allosteric connectivity in different degrees regarding signal transmission.
Article
Biochemistry & Molecular Biology
Jared Sivinski, Duc Ngo, Christopher J. Zerio, Andrew J. Ambrose, Edmond R. Watson, Lynn K. Kaneko, Marius M. Kostelic, Mckayla Stevens, Anne-Marie Ray, Yangshin Park, Chunxiang Wu, Michael T. Marty, Quyen Q. Hoang, Donna D. Zhang, Gabriel C. Lander, Steven M. Johnson, Eli Chapman
Summary: This study outlines the structural similarities and functional differences between ESKAPE GroES/GroEL and Escherichia coli GroES/GroEL, and reveals the importance of allosteric compatibility between these two proteins for cell viability. Interestingly, differences in allosteric compatibility do not necessarily result in differences in refolding rates.
Article
Chemistry, Multidisciplinary
Taylor K. Johnson, Daniel A. Bochar, Nathalie M. Vandecan, Jessica Furtado, Michael P. Agius, Sameer Phadke, Matthew B. Soellner
Summary: The study suggests that ATP-competitive inhibitors and allosteric inhibitors of Abl kinase do not exhibit synergy, but conformation-selective ATP-site inhibitors can have synergy with allosteric ABL inhibitors. The key driver for simultaneously binding two compounds to Abl kinase is the kinase conformation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Xuepeng Wei, Kathryn Kixmoeller, Elana Baltrusaitis, Xiaolu Yang, Ronen Marmorstein
Summary: Human G6PD plays a key role in maintaining cellular reduced glutathione, and NADP(+)s is crucial for stabilizing G6PD conformation and regulating G6P binding and catalysis. Cryo-electron microscopy structures of G6PD reveal that binding of NADP(+)s induces structural ordering and allosteric regulation. These findings have implications for understanding G6PD deficiencies and developing therapies for G6PD-mediated disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Juliana Rey, Maike Breiden, Vanda Lux, Anika Bluemke, Maike Steindel, Kamilla Ripkens, Bastian Moellers, Kenny Bravo Rodriguez, Prisca Boisguerin, Rudolf Volkmer, Joel Mieres-Perez, Tim Clausen, Elsa Sanchez-Garcia, Michael Ehrmann
Summary: This study reports a novel and reversible mechanism of protease activation, where an inactive protease serves as the activator. This mechanism involves the formation of an allosteric complex between HTRA1 and calpain 2, and exhibits activity only towards specific conformations of substrates. These findings have important implications for understanding protein quality control and potential side effects of drug modulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Computer Science, Artificial Intelligence
Hao Tian, Xi Jiang, Peng Tao
Summary: Allostery plays a crucial role in regulating protein activity, and identifying allosteric sites is essential for drug development. The ensemble learning method presented in this study shows good performance in predicting allosteric sites, with 84.9% accuracy in the test set.
MACHINE LEARNING-SCIENCE AND TECHNOLOGY
(2021)
Article
Biochemical Research Methods
Erin Skeens, George P. Lisi
Summary: The sensitivity of NMR chemical shift to local environment allows it to be used as a probe to study atomic level changes in proteins. Recent advancements in solution and solid-state NMR spectroscopy have utilized the chemical shift to investigate couplings between amino acids and establish networks of residues involved in allosteric pathways. The reciprocal sensitivity of thermodynamically and functionally coupled regions in a protein has made NMR spectroscopy a leading method for studying protein allostery.
Article
Biology
Juan Xie, Weilin Zhang, Xiaolei Zhu, Minghua Deng, Luhua Lai, Shozeb Haider
Summary: Allostery plays a fundamental role in biological processes, but predicting the impact of allosteric mutations, modifications, and effector binding on protein function is challenging. We developed a novel computational method, KeyAlloSite, to predict allosteric sites and identify key allosteric residues based on the evolutionary coupling model. Our predictions are consistent with previous experimental studies and key cancer mutations. KeyAlloSite can be applied in studying the evolution of protein allosteric regulation, designing and optimizing allosteric drugs, and performing functional protein design and enzyme engineering.
Article
Chemistry, Multidisciplinary
Elena Shanina, Sakonwan Kuhaudomlarp, Kanhaya Lal, Peter H. Seeberger, Anne Imberty, Christoph Rademacher
Summary: Carbohydrate-binding proteins, specifically lectins, are promising targets in drug discovery for combating antimicrobial resistance, yet non-carbohydrate drug-like inhibitors are still lacking. A druggable pocket in a beta-propeller lectin from Burkholderia ambifaria has been identified as a potential target for allosteric inhibitors. Future drug-discovery efforts focusing on small molecule inhibitors could benefit from targeting allosteric sites in lectins to combat antibiotic-resistant pathogens.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Zhongjie Han, Zhixiang Wu, Weikang Gong, Wenxue Zhou, Lei Chen, Chunhua Li
Summary: This study investigates the dynamic characteristics of PTB in its RNA-bound states using molecular dynamics simulation and other methods. The results provide insights into the stability of PTB upon RNA binding and the effect of specific mutations on the stability of the complex. The study also reveals the pre-encoded allosteric signal and the mechanism of signal transmission. These findings contribute to the understanding of PTB allostery and RNA recognition and have implications for drug design.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Federica Maschietto, Erik Zavala, Brandon Allen, J. Patrick Loria, Victor Batista
Summary: In this study, computational modeling and solution NMR spectroscopy were combined to identify an allosteric site in MptpA. The findings suggest that this site plays a crucial role in substrate binding and reaction kinetics.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Farindra Kumar Mahto, Akash Bhattacharya, Swati Bhattacharya
Summary: The Hsp70 chaperone protein system is crucial for protein folding and homeostasis. Molecular dynamics simulations reveal that the Lid domain has greater conformational flexibility than previously expected.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Deniz Dogan, Merve Arslan, Tugce Ulucay, Sibel Kalyoncu, Stefan Dimitrov, Seyit Kale
Summary: The study investigates the structural rearrangements of CENP-A nucleosomes resulting from antibody binding, showing that the antibodies can alter the dynamics of the nucleosomal core and indirectly affect the surrounding DNA. The binding of antibodies to the histone octamer surface is associated with conformational changes in CENP-A nucleosomes, indicating a more drastic impact compared to canonical nucleosomes. In addition, evidence suggests that the antibodies bind different octamer facades at varying affinities, revealing another level of complexity in DNA sequence regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
