Article
Multidisciplinary Sciences
Amitesh Anand, Arjun Patel, Ke Chen, Connor A. Olson, Patrick Phaneuf, Cameron Lamoureux, Ying Hefner, Richard Szubin, Adam M. Feist, Bernhard O. Palsson
Summary: In this study, the authors examined the systems level properties of the aerobic electron transport system using adaptive laboratory evolution and multi-omics analyses.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Alexander A. Vinogradov, Masanobu Nagano, Yuki Goto, Hiroaki Suga
Summary: The study reports two strategies for direct access to diverse ED substrates, revealing that EDs are uniquely promiscuous enzymes capable of performing retro-Michael reaction and engaging in nonspecific hydrophobic interactions with substrates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Maike Stegen, Andrea Engler, Crista Ochsenfarth, Iris Manthey, Jurgen Peters, Winfried Siffert, Ulrich H. Frey
Summary: The study characterized the human GRK6 promoter and found that the CREB binding site influenced promoter activity. Stimulation with a PKC activator led to decreased GRK6 expression at mRNA and protein levels, suggesting PKC might play a role in regulating GRK6 expression.
Article
Biochemistry & Molecular Biology
Cecilia Astigiano, Francesco Piacente, Maria Elena Laugieri, Andrea Benzi, Christian A. A. Di Buduo, Carolina P. P. Miguel, Debora Soncini, Michele Cea, Antonella Antonelli, Mauro Magnani, Alessandra Balduini, Antonio De Flora, Santina Bruzzone
Summary: SIRT6, a member of the sirtuin family, plays an emerging role in anti-inflammatory processes in various diseases and cell types, including endothelial cells. Overexpression of SIRT6 in human umbilical vein endothelial cells (SIRT6+ HUVECs) was found to affect adhesion molecule levels and promote megakaryocyte proliferation and proplatelet formation. Furthermore, the pro-inflammatory activation of the ATP/purinergic axis was reduced in SIRT6+ HUVECs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Takahiro Kosugi, Tatsuya Iida, Mikio Tanabe, Ryota Iino, Nobuyasu Koga
Summary: Allostery allows for the coordinated function of protein complexes by facilitating cooperative interaction between subunits. This study presents an approach to artificially create allosteric sites in protein complexes. By restoring the lost functions of pseudo-active sites, it is possible to generate allosteric sites within certain protein complexes. Computational design was used to restore ATP-binding ability in the pseudo-active site of the B subunit of V-1-ATPase. Single-molecule experiments with X-ray crystallography analysis demonstrated that binding of ATP to the designed allosteric site enhances the activity of V-1 and allows for modulation of rotation rate through ATP's binding affinity. This approach holds promise for programmable allosteric control of protein complex functions.
Article
Biochemistry & Molecular Biology
Carlos Santolaria, Diego Velazquez, Marcel Albacar, Antonio Casamayor, Joaquin Arino
Summary: The function of the Ppz1 phosphatase in Saccharomyces cerevisiae is controlled by its inhibitory subunit Hal3. Hal3 is a moonlighting protein involved in the CoA biosynthetic pathway. Deletion or specific mutations in a region of Hal3's N-terminal extension compromise its function as a Ppz1 inhibitor without affecting its ability to interact with the phosphatase. The presence of a specific sequence explains the unexpected ability of Cab3 to regulate Ppz1 function in Candida albicans. This study contributes to our understanding of Ppz phosphatase regulation and its importance in pathogenic fungi.
Article
Multidisciplinary Sciences
Andrija Sente, Rooma Desai, Katerina Naydenova, Tomas Malinauskas, Youssef Jounaidi, Jonas Miehling, Xiaojuan Zhou, Simonas Masiulis, Steven W. Hardwick, Dimitri Y. Chirgadze, Keith W. Miller, A. Radu Aricescu
Summary: In this study, the structures and arrangement diversity of GABA(A)Rs receptors were determined using cryogenic electron microscopy. It was found that different arrangements can affect receptor responses to modulators and that GABA(A)Rs receptors can simultaneously respond to two neurotransmitters. Through calculations and simulations, the researchers propose that differential assembly is a mechanism for regulating the function of GABA(A)Rs.
Article
Chemistry, Multidisciplinary
Nir Hananya, Sara K. Daley, John D. Bagert, Tom W. Muir
Summary: The study developed a efficient semi-synthesis method to create full-length ADP-ribosylated histones H3 and H2B, which were used to investigate the roles of histone ADP-ribosylation in DNA damage response. The results showed that ADP-ribosylation of serine-6 of histone H2B inhibits chromatin folding and higher-order organization, providing new insights into the impact of histone modifications on chromatin structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Stephen T. Hallett, Isabella Campbell Harry, Pascale Schellenberger, Lihong Zhou, Nora B. Cronin, Jonathan Baxter, Thomas J. Etheridge, Johanne M. Murray, Antony W. Oliver
Summary: The Smc5/6 complex plays a crucial role in recombination and virus replication prevention. The cryo-EM structure reveals the architectural overview of the complex and the binding of the Nse1/3/4 subcomplex to the SMC protein core. The interaction between Smc5 and Nse1 through the head domain is essential, and mutations in the Nse1 region result in growth defects and reduced chromatin association of the Smc5/6 complex.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Zhizeng Sun, Timothy Palzkill
Summary: The study identified essential active-site residues of the MCR-1 enzyme using deep sequencing, which are critical for its polymyxin resistance function. Approximately 75% of the residues examined were found to be essential for the enzyme's function, suggesting inhibitors binding near these sites will broadly inhibit MCR-1 and similar enzymes.
Article
Multidisciplinary Sciences
Khanh Vu Huu, Rene Zangl, Jan Hoffmann, Alicia Just, Nina Morgner
Summary: The study investigates the assembly process of F-1 complex from Acetobacterium woodii using laser induced liquid bead ion desorption mass spectrometry. The results indicate that nucleotide binding is crucial for in vitro assembly of F-1, while ATP hydrolysis is less critical. The study also proposes a model for the assembly pathway of a functional F-1 complex, correlating the results with activity measurements.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Ralf Schmauder, Thomas Eick, Eckhard Schulz, Guenther Sammler, Elmar Voigt, Guenter Mayer, Holger Ginter, Guenter Ditze, Klaus Benndorf
Summary: By using a microfluidic chip-based technique, we have developed a method for studying ion currents and fluorescence signals in order to measure the kinetics of channel activation and deactivation, as well as ligand binding and unbinding. This approach allows for the rapid generation of concentration-activation relationships and activation kinetics, while minimizing the effects of interference.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Frederik Rostrup, Christina B. Falk-Petersen, Kasper Harpsoe, Stine Buchleithner, Irene Conforti, Sascha Jung, David E. Gloriam, Tanja Schirmeister, Petrine Wellendorph, Bente Frolund
Summary: Research on DS2 analogues revealed that substituents at the 5-position of the imidazopyridine core scaffold greatly affect delta-selectivity and pharmacological profile. Among them, analogue 30 showed at least 60-fold selectivity for the α4β1δ receptor subtype, indicating a potential tool for selective characterization of delta-containing GABA(A)Rs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lea El Khoury, David L. Mobley, Dongmei Ye, Susan B. Rempe
Summary: The study predicted the binding mode of organophosphorus hydrolase with paraoxon using docking and molecular dynamics, identifying three hot-spot residues involved in the stability of the active site. Experimental results showed specific mutants exhibited enhanced substrate binding affinity for paraoxon.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Zhiyi Wu, Gabriel Kuteyi, Jiandong Huo, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The proton-coupled solute carriers PepT1 and PepT2 in the SLC15 family are crucial for acquiring dietary nitrogen and have extreme substrate promiscuity. Recent studies on their structure and function provide insights into their potential applications in drug development.