Article
Biochemistry & Molecular Biology
Philipp J. Heckmeier, Jeannette Ruf, David Buhrke, Brankica G. Jankovic, Peter Hamm
Summary: The protein MCL-1 is essential in regulating apoptosis in various cancers by binding to BIM according to an induced fit mechanism, leading to a cascade of structural rearrangements across a wide range of time scales.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paul Campitelli, Liskin Swint-Kruse, S. Banu Ozkan
Summary: Substitutions at nonconserved protein positions can have noncanonical and long-distance effects on protein function, potentially resulting from changes in the internal protein communication network and structural flexibility. Substitutions were found to have long-range effects on flexibilities and dynamic coupling of DNA-binding positions, with the degree of flexibility change correlating with experimentally measured changes in DNA binding. This study proposes that long-range and noncanonical substitution outcomes arise from rewiring long-range communication among functionally important positions.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Bethany Kolbaba-Kartchner, I. Can Kazan, Jeremy H. Mills, S. Banu Ozkan
Summary: The study explores the relationship between protein dynamics and enzymatic function in beta-lactamases, revealing that allosteric coupling of rigid residues to the active site has profound effects on enzyme function. By altering the dynamic profile of TEM-1 using computational protein design methods, it was found that changing residues surrounding highly coupled rigid residues significantly affected enzymatic activity and stability. This integration of computational protein design methods with analyses of protein dynamics represents a general approach to extend understanding of the relationship between dynamics and function in other enzyme classes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Tadeo Saldano, Nahuel Escobedo, Julia Marchetti, Diego Javier Zea, Juan Mac Donagh, Ana Julia Velez Rueda, Eduardo Gonik, Agustina Garcia Melani, Julieta Novomisky Nechcoff, Martin N. Salas, Tomas Peters, Nicolas Demitroff, Sebastian Fernandez Alberti, Nicolas Palopoli, Maria Silvina Fornasari, Gustavo Parisi
Summary: By studying the performance of AlphaFold2 under the ensemble paradigm, it was found that AlphaFold2 performs well in predicting the holo form of proteins, but its performance deteriorates with increasing conformational diversity. There is a negative correlation between the main-chain flexibility associated with apo-holo pairs of conformers and the predicted local model quality score.
Article
Multidisciplinary Sciences
Giorgos Gouridis, Yusran A. Muthahari, Marijn de Boer, Douglas A. Griffith, Alexandra Tsirigotaki, Konstantinos Tassis, Niels Zijlstra, Ruixue Xu, Nikolaos Eleftheriadis, Yovin Sugijo, Martin Zacharias, Alexander Domling, Spyridoula Karamanou, Charalambos Pozidis, Anastassios Economou, Thorben Cordes
Summary: Novel biophysical tools have allowed exploration of protein structural dynamics and evolution, revealing how modifications of structural cores can lead to diversification of protein functions. The mechanism uncovered in this study provides insights into the emergence of functional promiscuity during long periods of evolution, with implications for a wide range of domain architectures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Igors Dubanevics, Tom C. B. McLeish
Summary: Elastic Network Models (ENMs), a family of coarse-grained models for protein dynamics, require careful parameter selection to accurately represent experimental measurements or fully-atomistic simulations. This study investigates the effects of varying distance, mode cutoffs, and backbone stiffness on the dynamical structure of three proteins, and provides several important findings.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
I. Can Kazan, Jeremy H. Mills, S. Banu Ozkan
Summary: We investigated the relationship between mutations and dynamics in Escherichia coli dihydrofolate reductase (DHFR) using computational methods. Our study used molecular dynamics simulations and developed position-specific metrics to analyze the dynamics of wild-type DHFR. We found a significant association between dynamic flexibility and mutational tolerance of DHFR positions, and identified residues that control the dynamics of specific loops. These findings can help predict functionally beneficial or detrimental substitutions and guide rational enzyme engineering.
Article
Biochemistry & Molecular Biology
Jamie VanPelt, Shannon Stoffel, Michael W. Staude, Kayla Dempster, Heath A. Rose, Sarah Graney, Erin Graney, Sara Braynard, Elizaveta Kovrigina, David A. Leonard, Jeffrey W. Peng
Summary: This study reveals the real-time deactivation mechanisms of carbapenem-hydrolyzing beta-lactamase OXA-24/40 in Acinetobacter baumannii using NMR. The enzyme was found to have two deactivation mechanisms stemming from distinct active site environments, with mutagenesis showing that a conserved active site arginine stabilizes the environment for beta-lactone formation. These results have implications for the broader family of carbapenem-hydrolyzing beta-lactamases in clinical settings globally.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jennifer Y. Cui, George P. Lisi
Summary: Cytokines play a key role in cellular communication and biological regulation. Their timing, quantity, and localization are crucial in producing specific biological outcomes. Through molecular observation, insights gained may complement a system-level understanding of cytokine biology, explaining the diversity of downstream signaling events and informing therapeutic and experimental development.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Helen B. Belato, George P. Lisi
Summary: The discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPRs (Acrs), has revolutionized the field of CRISPR-Cas technology. These inhibitors have diverse structures and functions, and can act as orthosteric or allosteric inhibitors, as well as modify CRISPR-Cas components. Understanding the mechanisms of Acrs is crucial for the development of more precise and controllable CRISPR-Cas tools.
Article
Multidisciplinary Sciences
Lukas Rohland, Roman Kityk, Luka Smalinskaite, Matthias P. Mayer
Summary: The 70 kDa heat shock proteins (Hsp70s) are versatile molecular chaperones that assist in protein-folding processes. ATP and cochaperones induce structural rearrangements in Hsp70, with peptides causing larger changes and protein clients being more effective in stimulating ATP hydrolysis. The study provides insights into the mechanics, allostery, and dynamics of Hsp70 chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Dennis S. Winston, Scott D. Gorman, David D. Boehr
Summary: Conformational fluctuations are important for protein function and allosteric regulation. In this study, NMR experiments were used to investigate the conformational dynamics of ScCM. The results suggest that the two-state MWC model is insufficient to explain the conformational dynamics of ScCM, and tyrosine and tryptophan have different effects on the conformational fluctuations.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
I. Can Kazan, Prerna Sharma, Mohammad Imtiazur Rahman, Andrey Bobkov, Raimund Fromme, Giovanna Ghirlanda, S. Banu Ozkan
Summary: We developed an ICDC approach to identify, mutate, and assess distal sites to modulate protein function through co-evolution and dynamic coupling. The approach was validated using mutational fitness data of TEM-1 beta-lactamase and applied to identify positions and mutations in cyanovirin-N (CV-N) that can modulate binding affinity. The computational and experimental analyses revealed that the identified mutants impact the dynamics of the binding pocket and compensate for the entropic cost of binding. This work provides insights into the mechanism of distal mutations in regulating protein function and offers a blueprint for optimizing function through mutagenesis.
Article
Chemistry, Multidisciplinary
Rongying Liu, Long Li, Shuyu Chen, Zhiwei Yang, Zdravko Kochovski, Shilin Mei, Yan Lu, Lei Zhang, Guosong Chen
Summary: A protein assembly capable of switching interplay modes of multiple driving forces has been successfully achieved by leveraging ligand-ligand interaction and protein-protein interaction. This strategy not only provides a nanoscale understanding on the mechanism underlying the switch of interplay modes in the context of biomacromolecules, but also may enable the fabrication of diverse sophisticated biomacromolecular nanostructures that are historically inaccessible for conventional self-assembly strategies.
Article
Biochemistry & Molecular Biology
Till El Harrar, Benedikt Frieg, Mehdi D. Davari, Karl-Erich Jaeger, Ulrich Schwaneberg, Holger Gohlke
Summary: This study investigates the impact of aqueous ionic liquids on a model enzyme through molecular dynamics simulations and finds that they can affect enzyme activity by modifying local structural stability, eventually leading to perturbations in the catalytic site and protein core. The identification of perturbation pathways and specific interactions with IL ions helps predict variant libraries with improved tolerance to aqueous ionic liquids.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Joshua E. Mayfield, Shuang Fan, Shuo Wei, Mengmeng Zhang, Bing Li, Andrew D. Ellington, Felicia A. Etzkorn, Yan Jessie Zhang
ACS CHEMICAL BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Felicia A. Etzkorn, Song Zhao
ACS Chemical Biology
(2015)
Article
Oncology
Peibin Yue, Francisco Lopez-Tapia, David Paladino, Yifei Li, Chih-Hong Chen, Andrew T. Namanja, Tyvette Hilliard, Yuan Chen, Marcus A. Tius, James Turkson
Article
Multidisciplinary Sciences
Xingguo R. Chen, Shuang A. Fan, Rachel I. Ware, Felicia A. Etzkorn
Article
Biochemistry & Molecular Biology
Andrew T. Namanja, Jianghai Wang, Ralf Buettner, Loren Colson, Yuan Chen
JOURNAL OF MOLECULAR BIOLOGY
(2016)
Meeting Abstract
Oncology
Andrew T. Namanja, Ralf Buettner, Richard Jove, Yuan Chen
Article
Environmental Sciences
Vanessa E. Melin, David W. Johnstone, Felicia A. Etzkorn, Terry C. Hrubec
ENVIRONMENTAL MONITORING AND ASSESSMENT
(2014)
Article
Multidisciplinary Sciences
Chih-Hong Chen, Andrew T. Namanja, Yuan Chen
NATURE COMMUNICATIONS
(2014)
Article
Chemistry, Physical
Felicia A. Etzkorn, Rachel I. Ware, Amanda M. Pester, Diego Troya
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Biochemistry & Molecular Biology
Andrew T. Namanja, Jia Xu, Haihong Wu, Qi Sun, Anup K. Upadhyay, Chaohong Sun, Steven R. Van Doren, Andrew M. Petros
JOURNAL OF BIOMOLECULAR NMR
(2019)
Article
Biochemistry & Molecular Biology
Christina S. Kim, Anne M. Brown, Tijana Z. Grove, Felicia A. Etzkorn
Summary: Novel consensus leucine-rich repeat proteins (CLRR4-8) based on the LRR domain of NOD-like receptors show promise in high-affinity binding to bacterial cell wall component MDP. The biphasic binding curves and docking studies suggest multi-MDP binding, indicating potential for future pathogen biosensor design.
Article
Chemistry, Medicinal
Jianwen Xu, Andrew Namanja, Siew Leong Chan, Chelsea Son, Andrew M. Petros, Chaohong Sun, Czeslaw Radziejewski, Peter M. Ihnat
Summary: This investigation highlighted the utility of nuclear magnetic resonance (NMR) as a multi-attribute method for the characterization of therapeutic antibodies. Comparing results from isothermal chemical denaturation (ICD) and NMR with standard methods provided insights into the conformational states of a model monoclonal antibody (mAb1) and its protein-protein interactions (PPI) in concentrated solutions at different pH levels. NMR analysis confirmed the dominant native state of mAb1 under formulation-relevant conditions and provided a deeper understanding of its conformation in concentrated solutions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Physical
Paul J. Arcoria, Rachel Ware, Sunny Makwana, Diego Troya, Felicia A. Etzkorn
Summary: Fluoro- and chloro-alkene mimics of Gly-Pro and Pro-Pro can participate in n ->pi* donation to stabilize PPII conformations, but are poor n.p* acceptors. Proteo-alkene mimics lack significant n ->pi* interactions, leading to unstable PPII-like geometries.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Felicia A. A. Etzkorn, Jamie L. L. Ferguson
Summary: Full integration of green chemistry into undergraduate curriculum is essential for preparing students for a sustainable future. This article discusses the reasons for curriculum change, institutions leading the way in integration efforts, and available textbooks for both classroom and laboratory. The authors emphasize the need to give college professors more time to revamp the curriculum and to value their efforts. They call on the chemistry education community to participate in these efforts immediately.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Chen Peng, Andrew T. Namanja, Eva Munoz, Haihong Wu, Thomas E. Frederick, Mitcheell Maestre-Martinez, Isaac Iglesias Fernandez, Qi Sun, Carlos Cobas, Chaohong Sun, Andrew M. Petros
Summary: Fragment-based drug discovery (FBDD) and validation of small molecule binders using NMR spectroscopy is an established and widely used method in the early stages of drug discovery. This article presents the development of software tools for analyzing 2D NMR data for FBDD and hit validation purposes.
JOURNAL OF BIOMOLECULAR NMR
(2023)