Article
Biochemistry & Molecular Biology
Zully Mora-Sierra, Gopika Gopan, Roger Chang, Deborah E. Leckband, Martin Gruebele
Summary: Research demonstrates that interactions with end-grafted PNIPAM films above the lower critical solution temperature (LCST) can increase the folding stability of enzymes, such as phosphoglycerate kinase (PGK). By comparing two protein mutants, it is found that protein adsorption on different densities of PNIPAM affects stabilization. Additionally, experiments on temperature-dependent kinetics suggest that PNIPAM mainly interacts with the protein surface to increase conformational entropy, rather than crowding the unfolded state of the protein.
Article
Biochemistry & Molecular Biology
Sonya Lee, Cynthia N. Okoye, Devin Biesbrock, Emily C. Harris, Katelyn F. Miyasaki, Ryan G. Rilinger, Megalan Tso, Kathryn M. Hart
Summary: Thermodynamic stability is an important constraint on protein evolution, but the molecular mechanisms by which stability-altering mutations impact fitness are not well understood. This study demonstrates that a prevalent mutation in TEM beta-lactamase, M182T, increases fitness by reducing proteolysis. The study also suggests that a synthetic mutation, M182S, can act as a global suppressor, and its absence in natural populations may be due to genetic inaccessibility rather than fundamental differences in stability or activity.
Article
Biochemistry & Molecular Biology
Leonore Novak, Maria Petrosino, Daniele Santorelli, Roberta Chiaraluce, Valerio Consalvi, Alessandra Pasquo, Carlo Travaglini-Allocatelli
Summary: A Phi value analysis was conducted on BRD2(2) to investigate its folding pathway, revealing that the C-terminal region serves as the initial folding nucleus, with the N-terminal region consolidating its structure later in the process. This indicates a hierarchical mechanism of protein folding with non-native interactions playing a significant role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Yitong Wang, Tingting Wang, Quanmin Chen, Weichang Zhou, Jeremy Guo
Summary: The interaction of protein drugs with the air-liquid interface is crucial for their stability in aqueous formulations. Nonionic surfactants are commonly used to improve the stability by addressing adsorption issues. However, the role of protein drugs in stability has been neglected. This study investigates the correlation between protein surface behavior and interfacial stability, finding that the adsorption ability of proteins should not be ignored compared to surfactants. These findings provide valuable insights for preformulation studies and formulation development of therapeutic proteins.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biophysics
Roja Hadianamrei, Mhd Anas Tomeh, Stephen Brown, Jiqian Wang, Xiubo Zhao
Summary: This study focused on the development and characterization of short cationic amphiphilic beta-sheet forming anticancer peptides. The peptides exhibited selective anticancer activity influenced by their surface activity and secondary structure in hydrophobic surfaces, leading to disruption of mitochondrial membranes and apoptosis. Insights gained from the study can be used to design new ACPs with improved anticancer activity and lower toxicity against normal cells.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Chemistry, Multidisciplinary
Wenbo Zhang, Mingwei Liu, Yang Wang, Xin Wang, Ruonan Wang, Shuyuan Li, Lanlan Yu, Feiyi Zhang, Chenxuan Wang
Summary: Transferring structural information from amino acid sequence to macroscale assembly is achieved by designing two synthetic peptides, QNL-His and QNL-Arg, with one amino acid substitution and using scanning tunneling microscopy (STM) to determine their folding structure and beta-sheet supramolecular organization. The structural variations in beta-strand length distribution between QNL-His and QNL-Arg lead to distinguishable outcomes in their beta-sheet assembled fibrils and phase transitions. The comparison of their structures and macroscopic properties reveals the role of assembly in amplifying the structural variations associated with a single-site mutation from a single-molecule scale to a macroscopic scale.
Article
Biochemistry & Molecular Biology
Renan Vergara, Tania Berrocal, Eva Isela Juarez Mejia, Sergio Romero-Romero, Isabel Velazquez-Lopez, Nancy O. Pulido, Haven A. Lopez A. Sanchez, Daniel-Adriano Silva, Miguel Costas, Adela Rodriguez-Romero, Rogelio Rodriguez-Sotres, Alejandro Sosa-Peinado, D. Alejandro Fernandez-Velasco
Summary: This article describes the ligand binding, conformational stability and folding kinetics of the Lysine Arginine Ornithine (LAO) binding protein from Salmonella thiphimurium and constructs corresponding to its two independent domains. The results reveal unexpected behavior of the continuous and discontinuous domains, indicating the crucial role of the continuous domain in nucleating folding.
Article
Biochemistry & Molecular Biology
Chiung-Fang Hsu, Kai-Chun Chang, Yi-Lan Chen, Po-Szu Hsieh, An- Lee, Jui-Yun Tu, Yu-Ting Chen, Jin-Der Wen
Summary: Programmed-1 ribosomal frameshifting in viruses and bacteria is stimulated by mRNA structures within the coding region. The RNA pseudoknot folds sequentially through upstream stem S1 and downstream stem S2, with S2 tending to be trapped in intermediates. Masking nucleotides can modulate mRNA refolding and facilitate the stable folding of native pseudoknots.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemical Research Methods
Chad D. Hyer, Hsien-Jung L. Lin, Connor T. Haderlie, Monica Berg, John C. Price
Summary: The structure of a protein defines its function and integrity, and quantifying protein folding stability (PFS) is crucial for understanding disease mechanisms. However, the lack of a user-friendly data processing tool has hindered PFS studies. We present C-Half, a user-friendly software with a graphical interface for calculating PFS, and expect its introduction to promote the usage of PFS in research.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Yesol Sapozhnikov, Jagdish Suresh Patel, F. Marty Ytreberg, Craig R. Miller
Summary: In this study, a statistical framework is developed to quantify the uncertainty of predicted protein stability changes using the computational tool FoldX. It is found that the precision of the model improves significantly when molecular dynamics simulation is incorporated into the FoldX workflow.
BMC BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Maria Conde-Gimenez, Javier Sancho
Summary: Phenylketonuria is an autosomal recessive disorder caused by PAH variants, and one current therapeutic approach is to use pharmacological chaperones to rescue the enzyme's physiological function. This study investigates the folding equilibrium of PAH to develop new pharmacological chaperones for different forms of the disease. The research shows that both urea and thermal-induced denaturation of PAH result in the accumulation of equilibrium unfolding intermediates, indicating potential targets for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Joseph L. Harman, Patrick N. Reardon, Shawn M. Costello, Gus D. Warren, Sophia R. Phillips, Patrick J. Connor, Susan Marqusee, Michael J. Harms
Summary: This study identified a mutation in S100A9 protein that simultaneously increased its stability and disrupted its natural ability to regulate Toll-like receptor 4. Structural analysis revealed that the mutation distorted the hydrophobic binding surface of the protein, leading to its functional impairment. Bioinformatic analysis further showed that Phe residues at both positions 37 and 63 are rarely found in S100A9 proteins from different organisms, suggesting that avoiding pathological stabilizing interactions constrains the evolution of S100A9.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ruiyue Tan, Margaret Hoare, Kevin A. Welle, Kyle Swovick, Jennifer R. Hryhorenko, Sina Ghaemmaghami
Summary: The folding of proteins during translation while bound to the ribosome is not well understood. This study developed a method using mass spectrometry to measure the stability of nascent polypeptide chains. The results showed that the ribosome significantly influences the stability of the nascent polypeptides, with variations depending on different folding domains and localized charge distributions within the polypeptides. The study suggests that electrostatic interactions between the ribosome and nascent polypeptides play a role in these stability modulations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Federica Agosta, Pietro Cozzini
Summary: Non-covalent intramolecular interactions are crucial for protein folding. Changes in amino acids, pH, or temperature can lead to misfolding or unfolding of proteins, resulting in functional impairment and pathological conditions. The recently implemented HINT scoring function is proposed as a rapid and sensitive method to evaluate destabilization processes. This study evaluates the stability of Transthyretin by generating mutated models under different pH conditions and comparing with experimental data, suggesting that the HINT scoring function can accurately and rapidly predict the effects of structural changes on protein systems.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Materials Science, Multidisciplinary
F. Caballero Briones, J. Guerrero-Contreras, S. E. Benito-Santiago, J. L. Sanchez Llamazares, F. J. Espinosa-Faller
Summary: This study observed the formation of nanoscrolls after hydrazine treatment in iron oxide-decorated graphene oxide, leading to the formation of nanoribbons after HCl treatment. The proposed mechanism includes the decoration onto the epoxy/hydroxyl moieties and the reduction of carboxyl and carbonyl groups causing the sheet rolling, with nanoribbons forming upon iron oxide dissolution and breaking of iron-carbon bonds. The superparamagnetic materials exhibited maximum saturation magnetization of 30 and 20 A.m(2).kg(-1), respectively, and the formation of these structures in FeOx-GO appears to be a more general phenomenon not described in other reports.
Article
Biochemistry & Molecular Biology
Bhishem Thakur, Archit Gupta, Purnananda Guptasarma
Summary: HU is a DNA-binding protein with a helical N-terminal region and a beta strand- and IDR-rich C-terminal region. It forms a dimer with extensive CTR-CTR contacts and a single-chain simulacrum, HU-Simul, is created to bind to dsDNA and cruciform DNA.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Hematology
Dina Stroopinsky, Jessica Liegel, Manoj Bhasin, Giulia Cheloni, Beena Thomas, Swati Bhasin, Ruchit Panchal, Haider Ghiasuddin, Maryam Rahimian, Myrna Nahas, Shira Orr, Marzia Capelletti, Daniela Torres, Cansu Tacettin, Matthew Weinstock, Lina Bisharat, Adam Morin, Kathleen M. Mahoney, Benjamin Ebert, Richard Stone, Donald Kufe, Gordon J. Freeman, Jacalyn Rosenblatt, David Avigan
Summary: The personalized leukemia vaccine, combining patient-derived leukemia cells with autologous dendritic cells, showed efficacy in expanding tumor-specific immunity. Utilizing a murine leukemia model, vaccination with dendritic cell/acute myeloid leukemia fusions in combination with checkpoint blockade treatment induced durable leukemia-specific immunity and protected against lethal tumor challenge. Long-term survivors exhibited increased T-cell clonal diversity and resistance to subsequent tumor challenge.
Article
Biochemistry & Molecular Biology
Bhishem Thakur, Kanika Arora, Archit Gupta, Purnananda Guptasarma
Summary: Researchers investigated whether the nucleoid-associated histone-like protein (HU) could act as a glue in biofilms, finding evidence through various experiments to support this hypothesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kanika Arora, Bhishem Thakur, Archit Gupta, Purnananda Guptasarma
Summary: In enteric bacteria like Escherichia coli, there are two homologs of the DNA-binding nucleoid associated protein (NAP) known as HU, which exist in different forms and dominate different stages of bacterial growth. Due to similarities in their properties and the difficulty in purifying them separately, these dimeric forms can interfere with each other. The creation of a functional analog of HU-AB, termed HU-B-A, solves this problem by combining HU-B and HU-A chains into a single polypeptide with a higher stability and dominance in mixtures.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kanika Arora, Bhishem Thakur, Arpita Mrigwani, Purnananda Guptasarma
Summary: The study explores the impact of N-terminal extensions on the conversion of homodimers into heterodimers of bacterial nucleoid-associated protein HU. Results suggest that these extensions interfere with the spontaneous formation of heterodimers and that direct chain interactions facilitated by proximal genes can promote heterodimer formation in vivo. The mechanism underlying this interference involves the molecular structure of the protein at its dimeric interface.
Article
Biochemistry & Molecular Biology
Manni Luthra-Guptasarma, Purnananda Guptasarma
Summary: The authors propose that hyper-inflammation is more likely to occur in individuals with pre-existing chronic inflammation due to the presence of factors that limit viral proliferation and suppressed anti-inflammatory mechanisms. They suggest that avoiding foods that promote chronic inflammation and adopting foods that suppress chronic inflammation may reduce susceptibility to hyper-inflammation in COVID-19 and other viral diseases.
Article
Multidisciplinary Sciences
Georgios Theocharidis, Beena E. Thomas, Debasree Sarkar, Hope L. Mumme, William J. R. Pilcher, Bhakti Dwivedi, Teresa Sandoval-Schaefer, Ruxandra F. Sirbulescu, Antonios Kafanas, Ikram Mezghani, Peng Wang, Antonio Lobao, Ioannis S. Vlachos, Biraja Dash, Henry C. Hsia, Valerie Horsley, Swati S. Bhasin, Aristidis Veves, Manoj Bhasin
Summary: This study utilizes single-cell RNA sequencing to reveal the distribution of specific populations of fibroblasts and macrophages in diabetic foot ulceration (DFU) patients and identifies their crucial roles in wound healing.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Bhakti Dwivedi, Hope Mumme, Sarthak Satpathy, Swati S. Bhasin, Manoj Bhasin
Summary: Survival Genie is an online tool for survival analysis based on single-cell RNA-seq and other molecular inputs. It contains multiple cancer datasets and supports various analysis options.
SCIENTIFIC REPORTS
(2022)
Article
Biotechnology & Applied Microbiology
Arpita Mrigwani, Madhav Pitaliya, Harman Kaur, Bharathraj Kasilingam, Bhishem Thakur, Purnananda Guptasarma
Summary: Thermobifida fusca cutinase (TfCut2) is a carboxylesterase that can degrade polyethylene terephthalate (PET) and its degradation intermediates into terephthalic acid (TPA). By studying the surface comparisons of certain carboxylesterases and conducting simulations, 22 variants were designed for potential improvement in TPA generation from PET. Among these variants, 7 displayed increased activity against solid PET, with 4 of them surpassing the most-active mutant known till date. These improvements were attributed to changes in PET binding rather than catalytic efficiency.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Arpita Mrigwani, Bhishem Thakur, Purnananda Guptasarma
Summary: In the degradation of solid polyethylene terephthalate (PET) by leaf branch compost cutinase (LCC), the efficient binding of LCC onto the solid PET surface prevents the degradation intermediates (DIs) from converting into recyclable terephthalic acid (TPA) in solution. By introducing mutations to reduce LCC's binding to solid PET, the production of TPA increased by 3.6-fold due to the retention of enzyme in solution for degrading DIs. Additionally, the synergy between mutated LCC and wild-type LCC resulted in even higher yields of TPA with nearly 100% purity.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Archit Gupta, Ashish Joshi, Kanika Arora, Samrat Mukhopadhyay, Purnananda Guptasarma
Summary: The bacterial chromosome, known as its nucleoid, is an amorphous assemblage of globular nucleoprotein domains that exist as an irregularly-shaped, membrane-less, intracellular compartment separated from the cell's cytoplasm. Two abundant nucleoid-associated proteins, HU and Dps, undergo spontaneous complex coacervation with different forms of DNA/RNA, causing condensation and compaction of nucleic acids into liquid-liquid phase separated condensates in vitro. These complex coacervation modes may serve as models for understanding the in vivo relationships among nucleoid-associated proteins, explaining the presence of multiple isoforms of HU and the roles of HU and Dps in E. coli growth.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Hope Mumme, Beena E. Thomas, Swati S. Bhasin, Upaasana Krishnan, Bhakti Dwivedi, Pruthvi Perumalla, Debasree Sarkar, Gulay B. Ulukaya, Himalee S. Sabnis, Sunita I. Park, Deborah Deryckere, Sunil S. Raikar, Melinda Pauly, Ryan J. Summers, Sharon M. Castellino, Daniel S. Wechsler, Christopher C. Porter, Douglas K. Graham, Manoj Bhasin
Summary: This study utilizes single-cell RNA sequencing to analyze pediatric AML bone marrow samples and identifies a 7-gene signature that can distinguish malignant cells at diagnosis and is associated with relapse or complete remission.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lijun Yao, Reyka G. Jayasinghe, Brian H. Lee, Swati S. Bhasin, William Pilcher, Deon Bryant Doxie, Edgar Gonzalez-Kozlova, Surendra Dasari, Mark A. Fiala, Yered Pita-Juarez, Michael Strausbauch, Geoffrey Kelly, Beena E. Thomas, Shaji K. Kumar, Hearn Jay Cho, Emilie Anderson, Michael C. Wendl, Travis Dawson, Darwin D'souza, Stephen T. Oh, Giulia Cheloni, Ying Li, John F. DiPersio, Adeeb H. Rahman, Kavita M. Dhodapkar, Seunghee Kim-Schulze, Ravi Vij, Ioannis S. Vlachos, Shaadi Mehr, Mark Hamilton, Daniel Auclair, Taxiarchis Kourelis, David Avigan, Madhav V. Dhodapkar, Sacha Gnjatic, Manoj K. Bhasin, Li Ding
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Arpita Mrigwani, Bhishem Thakur, Purnananda Guptasarma
Summary: The synergy between two enzymes helps improve the degradation efficiency of PET, resulting in the production of pure terephthalic acid and ethylene glycol.
Article
Multidisciplinary Sciences
Pragya Prakash, Sanjeev Chandrayan, Purnima Tiwari, Hare Ram Singh, Santosh Kumar Jha
Summary: In this study, multiple bacterial strains were isolated from soil and water, screened for glutaminase-free L-asparaginase activity, and purified for further characterization. The optimal working pH for purification was found to be 8.6, resulting in a purity level of 99.2% for the L-asparaginase enzyme. This developed purification process and characterization could be instrumental for naturally occurring enzymes, as most current processes focus on recombinant enzymes.
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)