Article
Biochemistry & Molecular Biology
Bryan VanSchouwen, Stephen Boulton, Giuseppe Melacini
Summary: This study using NMR reveals that the contributions of the two substituents of cGMP to the binding affinity of PKG are surprisingly nonadditive, primarily due to mutual protein-ligand conformational selection. The 6-oxo substituent controls the conformational equilibrium of the bound protein, while the 2-NH2 substituent primarily controls the conformational equilibrium of the unbound ligand. Understanding the conformational dynamics of both the protein and ligand is essential to explain the cGMP-versus-cAMP selectivity of PKG.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mariia Khamina, Karla Martinez Pomier, Madoka Akimoto, Bryan VanSchouwen, Giuseppe Melacini
Summary: The protein kinases PKA and PKG can be activated by not only cyclic nucleotides, but also a wide range of non-canonical allosteric effectors. The molecular mechanisms involve shifts in dynamical regulatory equilibria and modulation of inter-protomer interactions. Mutations can lead to constitutive kinase activation, resulting in physiological or pathological outcomes.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Microbiology
Hwan Youn, Marcus Carranza
Summary: The active and inactive structures of the Escherichia coli cAMP receptor protein (CRP) were compared to establish a model for the cAMP-induced activation of CRP. This model is consistent with biochemical studies of CRP and CRP* mutants. The cAMP affinity and specificity of CRP and CRP* mutants are determined by the effectiveness of the cAMP pocket and the protein equilibrium of apo-CRP. The review also highlights current understanding and knowledge gaps in CRP-DNA interactions and identifies important future research directions.
JOURNAL OF MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
David P. Tilly, David T. J. Morris, Jonathan Clayden
Summary: In this study, it was discovered that the ethylene-bridged hydrogen-bonded urea oligomer linear chain has reversible anion coordination and cascade conformational changes. The polarity reversals of hydrogen bonds in the oligomer propagate, resulting in a global switch of hydrogen-bond directionality. This induces a change in emission and excitation wavelengths of a fluorophore at the opposite terminus. Consequently, the molecule acts as a chemical sensor with a relayed remote spectroscopic response to varying anion concentrations. The anion-induced polarity switch provides an artificial communication mechanism for conveying information through oligomeric structures.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biophysics
Hebatallah Mohamed, Ubaidullah Baryar, Amir Bashiri, Rajeevan Selvaratnam, Bryan VanSchouwen, Giuseppe Melacini
Summary: Allosteric regulation is crucial for controlling biological functions and allosteric sites are promising for selective drug targeting. However, accurately mapping allosteric sites remains challenging. This study introduces two new CHESCA-based methodologies, T-CHESCA and CLASS-CHESCA, to narrow down allosteric maps to core residues. Both methods rely on the invariance of core inter-residue correlations to changes in chemical shifts. The results provide a toolset for prioritizing and analyzing allosteric sites and have implications for disease-related mutations and the design of selective allosteric modulators.
BIOPHYSICAL JOURNAL
(2022)
Review
Biology
Ronja Reinhardt, Thomas A. Leonard
Summary: Phosphorylation of proteins is a common mechanism for regulating their function, localization, or activity. Protein kinases, which use ATP to phosphorylate protein substrates, are important signal transducers in cells. The mechanism of phosphoryl-transfer is conserved among protein kinases, and the precise mechanism of autophosphorylation is still a topic of debate. In this review, we evaluate different proposed mechanisms of autoregulation in protein kinases and discuss their implications in physiological signaling networks.
Review
Mathematical & Computational Biology
Nikolay Dokholyan
Summary: The advancement in protein design has led to the potential development of a nanoscale programming language, utilizing molecules as operands and their conformational states as logic gates. By harnessing natural evolutionary processes, code can evolve during computation, leading to revolutionary algorithmic developments with wide-ranging impacts on biotechnological applications. NCAs based on single-chain proteins have the ability to revolutionize studies of biological systems and enable deeper understanding of human biology and disease.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2021)
Article
Immunology
Kaiying Wang, Huifang Lu, Mei Zou, Guangli Wang, Jiajun Zhao, Xiaoyu Huang, Fangyu Ren, Huaqin Hu, Jian Huang, Xun Min
Summary: This study reveals the role of DegS in regulating the antioxidant capacity of Vibrio cholerae through the cAMP-CRP-RpoS pathway. Deletion of the degS gene attenuates the antioxidant capacity of V. cholerae, and the overexpression of XthA partially compensates for this deficiency. In addition, degS, rpoE, and rpoS gene deletions are associated with reduced resistance to oxidative stress and colonization ability in a mouse intestine experiment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Yuchang Di, Siyue Xu, Mingzhe Chi, Youwei Hu, Xiao Zhang, Honghai Wang, Wenhong Zhang, Xuelian Zhang
Summary: The acetylation of CRP K193 in Mycobacterium tuberculosis (Mtb) modulates its DNA-binding ability, affects mycobacterial growth and stress response, and regulates the expression of relevant genes. The reversible acetylation of CRP K193 is mediated by AcP and NAD(+)-dependent deacetylases. These findings contribute to a better understanding of the survival and pathogenicity of mycobacteria.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Caitlin Walker, Yingjie Wang, Cristina Olivieri, V. S. Manu, Jiali Gao, David A. Bernlohr, Davide Calebiro, Susan S. Taylor, Gianluigi Veglia
Summary: Somatic mutations in the PRKACA gene lead to the development of Cushing's syndrome, with the E31V allosteric mutation disrupting communication nodes and nucleotide-substrate binding cooperativity. The loss of binding cooperativity in Cushing's syndrome mutants is proportional to the density of the intramolecular allosteric network, suggesting a common mechanism for this disease.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemical Research Methods
Yigang Chen, Yang-Chi-Dung Lin, Yijun Luo, Xiaoxuan Cai, Peng Qiu, Shidong Cui, Zhe Wang, Hsi-Yuan Huang, Hsien-Da Huang
Summary: A novel CRP-binding site prediction model called CRPBSFinder was developed in this research, which combined the hidden Markov model, knowledge-based PWMs and structure-based binding affinity matrixes. The model showed higher prediction performance compared to classic methods and quantitatively indicated the binding affinity of transcription factor binding sites. The prediction result included both known regulated genes and 1089 novel CRP-regulated genes.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Microbiology
Shweta Chakraborty, Parul Singh, Aswin Sai Narain Seshasayee
Summary: Different genes show different trends in response to various transcription factor concentrations. This study demonstrates the use of phenomenological models to analyze transcription factor concentration-dependent genome-wide expression data, providing greater insights and enhancing the interpretability of classical clustering methods.
Article
Multidisciplinary Sciences
Jia-Yong Zhong, Longjian Niu, Zhuo-Bin Lin, Xin Bai, Ying Chen, Feng Luo, Chunhui Hou, Chuan-Le Xiao
Summary: By using the high-throughput Pore-C technique, researchers have discovered extensive and regionally restricted clusters of single-allele topologies in two human cell types, which aggregate into canonical 3D genome structures. They also observed a significant portion of multi-contact reads spanning multiple compartments of the same chromatin type over long distances. Moreover, the single-allele topology clusters are cell type-specific. These findings provide global characterization of single-allele topologies and reveal the principles of genome folding.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Laurel Pegram, Demian Riccardi, Natalie Ahn
Summary: Using long molecular dynamics simulations, this study reveals the unexpected flexibility of the A-loop in ERK2 kinase and its coupling with the active site dynamics. The simulations show distinct conformational states of the A-loop in both phosphorylated and unphosphorylated forms, with the phosphorylated form exhibiting restrained dynamics and reduced mobility in the active site. These findings enhance our understanding of ERK2 regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Urology & Nephrology
Zhiheng Liu, Yunjing Liu, Lin Dang, Meijuan Geng, Yongzhan Sun, Yi Lu, Zhongze Fang, Hui Xiong, Yupeng Chen
Summary: Genome-wide mapping and transcriptomic analysis revealed the mechanism of CREB in ADPKD, showing its activation of ribosome biogenesis genes promoting cystogenesis. The integrated analysis concluded that CREB is closely associated with cyst growth.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Editorial Material
Cell Biology
Ayman M. Mahmoud, M. Yvonne Alexander, Yusuf Tutar, Fiona L. Wilkinson, Alessandro Venditti
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2017)
Article
Chemistry, Inorganic & Nuclear
Elvan Ustun, Aykut Ozgur, Kubra A. Coskun, Serpil Demir Dusunceli, Ismail Ozdemir, Yusuf Tutar
TRANSITION METAL CHEMISTRY
(2017)
Editorial Material
Respiratory System
Esen Tutar, Yusuf Tutar
JOURNAL OF THORACIC DISEASE
(2019)
Review
Biochemistry & Molecular Biology
Magdalena Rudzinska, Alessandro Parodi, Surinder M. Soond, Andrey Z. Vinarov, Dmitry O. Korolev, Andrey O. Morozov, Cenk Daglioglu, Yusuf Tutar, Andrey A. Zamyatnin
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Oncology
Mustafa Ergul, Fugen Aktan, Mehmet T. Yildiz, Yusuf Tutar
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Kubra A. Coskun, Irfan Koca, Mehmet Gumus, Yusuf Tutar
Summary: The research aimed to design a novel HSP70 inhibitor, KBR1307, which can bind to HSP70 in the presence and absence of nucleotides, effectively inhibit HSP70 activity, and display a lower IC50 value in the MCF-7 cell line compared to PES. This suggests that KBR1307 may be a more promising template for novel anticancer drug development.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Andrology
Cengiz Guney, Kubra Acikalin Coskun, Yusuf Tutar
Summary: Testicular torsion leads to tissue damage, with HSPs playing an important role in the process. Omeprazole was found to effectively alleviate lipid peroxidation and DNA damage levels, promoting testicular torsion recovery.
Editorial Material
Biochemistry & Molecular Biology
Yusuf Tutar
CURRENT MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Altan Kara, Aykut Ozgur, Saban Tekin, Yusuf Tutar
Summary: This study investigated the relationship between differentially expressed genes affecting patient survival and the mechanism of drug resistance in non-small cell lung adenocarcinoma. The results showed that several signaling pathways were associated with drug resistance in NSCLC cells.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Mustafa Ergul, Fugen Aktan, Yusuf Tutar
Summary: This study identified three loss-of-function mutants of Hsp70, which may affect the inhibition activity of drugs. Designing inhibitors by considering these critical residues may improve drug design and increase drug efficiency.
CURRENT PROTEOMICS
(2022)
Review
Oncology
Fahima Danesh Pouya, Yousef Rasmi, Irem Yalim Camci, Yusuf Tutar, Mohadeseh Nemati
Summary: Colorectal cancer is a highly prevalent cancer worldwide with no definitive cure. Targeted therapies and the effectiveness of chemotherapy drugs help improve patient survival rates. Capecitabine is commonly used in standard chemotherapy regimens for colorectal cancer, playing a significant role in combination therapies.
JOURNAL OF CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Irfan Koca, Volkan Kamaci, Ceylan Ozsoy, Yusuf Sert, Ibrahim Kani, Lutfi Tutar, Yusuf Tutar
Summary: Heat Shock Proteins (Hsps) play a major role in cancer onset. Cancer cells have a higher metabolic rate compared to normal cells, resulting in faster folding of substrate proteins. Hsps help cells survive and inhibit apoptosis, folding substrate proteins, especially signaling proteins. Dual inhibition of Hsp90 and Hsp70 potentially provides anti-cancer effects.
Article
Biochemistry & Molecular Biology
Mehmet Gumus, Irfan Koca, Yusuf Sert, Ali Disli, Ezgi Nurdan Yenilmez Tunoglu, Lutfi Tutar, Yusuf Tutar
Summary: Intensive studies are being conducted on hepatocellular carcinoma (HCC) due to the lack of effective preventive or curative treatments. Understanding the molecular mechanisms and combining drugs with molecular therapies has become crucial for HCC treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Emergency Medicine
Nese Kurt Ozkaya, Umut Zereyak, Kubra Acikalin Coskun, Yusuf Tutar, Sarper Yilmaz
ULUSAL TRAVMA VE ACIL CERRAHI DERGISI-TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY
(2020)
Article
Surgery
Mehmet Emre Coskun, Kubra Acikalin Coskun, Yusuf Tutar
PHOTOMEDICINE AND LASER SURGERY
(2018)
Review
Biochemistry & Molecular Biology
Kumaresan Ramanathan, Minale Fekadie, Giri Padmanabhan, Henok Gulilat
Summary: Long noncoding RNAs (lncRNAs) play critical roles in kidney disease development and their dysregulation can lead to various disease processes. Understanding the function and potential application of lncRNAs in kidney disease may provide new diagnostic and therapeutic opportunities. This review provides an overview of lncRNA characteristics, function, and specific studies related to kidney disease treatment.
CELL BIOCHEMISTRY AND FUNCTION
(2024)