Article
Biochemistry & Molecular Biology
Ish Kumar, Amin Sagar, Kanika Dhiman, Christopher R. Bethel, Andrea M. Hujer, Justin Carifi, Ashish, Robert Bonomo
Summary: Designing new beta-lactamase inhibitors (BLIs) is crucial to combat BL-mediated resistance. Small angle x-ray scattering (SAXS) in combination with molecular modeling can determine dynamic structures of macromolecules in solution and is useful in studying conformational changes in enzyme-inhibitor complexes. Our findings support the importance of exploring conformational changes using SAXS analysis in the design of future BLIs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Purbasha Nandi, Shan Li, Rod Carlo A. Columbres, Feng Wang, Dewight R. Williams, Yu-Ping Poh, Tsui-Fen Chou, Po-Lin Chiu
Summary: The study visualized the structures of p97(R155H) and p47 cofactor using single-particle cryo-EM, revealing that more than one-third of the population is in the dodecameric form. Presence of nucleotides dissociates the dodecamer into two hexamers, enhancing its function significantly. The N-domains of the p97(R155H) mutant display consistent configurations in ADP- or ATP gamma S-bound states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Balamurugan Dhayalan, Deepak Chatterjee, Yen-Shan Chen, Michael A. Weiss
Summary: Analysis of diabetes-associated mutations in the human insulin gene has provided insights into the folding mechanisms of proinsulin, revealing the impact of mutations on pancreatic beta-cell dysfunction and insulin secretion. Studies suggest that conserved residues play a crucial role in folding efficiency and the susceptibility of proinsulin to impaired foldability can contribute to the development of diseases. This highlights the molecular links between biophysical principles and the impact on diseases such as diabetes and obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Plant Sciences
Shengming Yang, Megan Overlander, Jason Fiedler
Summary: This study characterized and genetically mapped the gpa1.a mutation causing variegation in barley, identifying a potential candidate gene for Gpa1 in the PTOX-encoding gene in a delimited region. The findings provide a foundation for cloning Gpa1 and enhancing understanding of molecular mechanisms underlying chloroplast biogenesis in monocot plants.
Article
Multidisciplinary Sciences
Michelle S. Prew, Christina M. Camara, Thomas Botzanowski, Jamie A. Moroco, Noah B. Bloch, Hannah R. Levy, Hyuk-Soo Seo, Sirano Dhe-Paganon, Gregory H. Bird, Henry D. Herce, Micah A. Gygi, Silvia Escudero, Thomas E. Wales, John R. Engen, Loren D. Walensky
Summary: Prew et al. uncovered the structural basis for human VLCAD deficiency caused by point mutations in the enzyme's membrane-binding region, which disrupts membrane interaction and impairs homeostatic function. This study provides insights into the pathogenesis of VLCAD deficiency.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hyeon Jin Kim, Chang Woo Han, Mi Suk Jeong, Se Bok Jang
Summary: KRAS mutations are found in 25% of human cancers and play a role in diverse cellular processes. In this study, the peptide GJ101 was shown to bind directly to the KRAS mutant (G12V) and exhibited tumor-suppressive activity. The complex structure of KRAS and GJ101 was determined by X-ray crystallography, confirming the interaction between residue Q61 and GJ101. These findings suggest that GJ101 could serve as a potential inhibitor for KRAS G12V.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Oncology
Ana Sara Gomes, Helena Ramos, Alberto Inga, Emilia Sousa, Lucilia Saraiva
Summary: This article provides an integrated view of mutp53 regulation, particularly focusing on the structural traits of mutp53 and targeting agents capable of its reactivation, including their biological, biochemical and biophysical features.
Article
Biochemistry & Molecular Biology
Ahmed L. Alaofi
Summary: This study investigated the structural and functional differences between mouse and human DPP4 receptors using MD simulations and docking techniques. The results showed that a single Thr288Ala mutation induced conformational and flexibility changes, which could explain the functional differences between these two receptors against MERS-CoV.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Alexander Myasnikov, Hanwen Zhu, Patricia Hixson, Boer Xie, Kaiwen Yu, Aaron Pitre, Junmin Peng, Ji Sun
Summary: Mutations in LRRK2 are commonly associated with Parkinson's disease. This study provides insights into the physiological and pathological roles of LRRK2, and establishes a structural template for future therapeutic interventions in PD. The high-resolution structures of full-length human LRRK2 and COR-mediated LRRK2 dimers reveal key elements for rationalizing disease-causing mutations and potential targets for inhibitors.
Article
Biochemistry & Molecular Biology
Marat A. Mukhamedyarov, Aydar N. Khabibrakhmanov, Venera F. Khuzakhmetova, Arthur R. Giniatullin, Guzalia F. Zakirjanova, Nikita V. Zhilyakov, Kamilla A. Mukhutdinova, Dmitry V. Samigullin, Pavel N. Grigoryev, Andrey V. Zakharov, Andrey L. Zefirov, Alexey M. Petrov
Summary: Amyotrophic lateral sclerosis (ALS) is a disease characterized by skeletal muscle denervation, motor neuron loss, and respiratory failure. Mutations in the FUS gene are a common genetic cause of ALS, resulting in degeneration. In mutant FUS mice at the pre-onset stage, early structural and functional alterations in diaphragm neuromuscular junctions (NMJs) were observed. Lipid peroxidation and decreased lipid raft staining were found in the mutant mice. Despite preserved end-plate structure, increased levels of presynaptic proteins and impaired neurotransmitter release were observed in FUS mice. These findings suggest that alterations in membrane properties, synapsin 1 levels, and calcium kinetics could be early indicators of nascent NMJ pathology in ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Junaid, Cheng-Dong Li, Jiayi Li, Abbas Khan, Syed Shujait Ali, Syed Baber Jamal, Shah Saud, Arif Ali, Dong-Qing Wei
Summary: The study focused on the resistance mechanisms offered by mutations Q10P, D12A, and G97D in Pyrazinamidase. It was found that Q10P and D12A mutations disrupt the communication among the catalytic triad, affecting the formation of the oxyanion hole and reducing the binding affinity to the drug. These mutations destabilize the interaction between Fe2+ ion and specific residues, ultimately impacting the binding pocket volume and PZA binding. The study provides insight for the design of new and effective PZase inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biology
Metehan Ilter, Ramazan Kasmer, Farzaneh Jalalypour, Canan Atilgan, Ozan Topcu, Nihal Karakas, Ozge Sensoy
Summary: This study investigates the impact of phosphorylation on the dynamics of RAS proteins and demonstrates the regulation of HRAS mutant protein by small therapeutic molecules. The study shows that phosphorylation affects the RAS/RAF interface by distorting Switch I. Moreover, approved therapeutic molecules targeting Switch I can detach it from the nucleotide-binding pocket. In vitro experiments verify the computational findings.
Article
Biochemical Research Methods
Tyll Stocker, Lena Altrogge, Caroline Marcon, Yan Naing Win, Frank Hochholdinger, Heiko Schoof
Summary: Insertional mutagenesis is a powerful tool for creating loss-of-function mutations on a genome-wide scale. MuWU is an automated Mutant-seq workflow utility that efficiently identifies insertion sites and handles complex bioinformatic tasks, making it a valuable resource for functional genomics studies.
Article
Cell Biology
Amin Addetia, Young -Jun Park, Tyler Starr, Allison J. Greaney, Kaitlin R. Sprouse, John E. Bowen, Sasha W. Tiles, Wesley C. Van Voorhis, Jesse D. Bloom, Davide Corti, Alexandra C. Walls, David Veesler
Summary: The evolution of SARS-CoV-2 is weakening antibody responses from vaccination and prior infection. The E406W mutation in the receptor-binding domain of the virus alters the epitopes recognized by therapeutic monoclonal antibodies and vaccine-induced neutralizing antibodies. This highlights the structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging variants.
Article
Cell Biology
Raquel Garcia-Lopez, Ana Pombero, Alicia Estirado, Emilio Geijo-Barrientos, Salvador Martinez
Summary: Our study suggests that deleting the first coding exon of the Lis1 gene may cause cortical anomalies associated with the pathophysiology of schizophrenia. The Lis1/sLis1 murine model shows abnormal neuronal morphology and enhanced cortical excitability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)