Article
Biochemistry & Molecular Biology
Satchal K. Erramilli, Pawel K. Dominik, Dawid Deneka, Piotr Tokarz, Sangwoo S. Kim, Bharat G. Reddy, Blazej M. Skrobek, Olivier Dalmas, Eduardo Perozo, Anthony A. Kossiakoff
Summary: CorA is a primary magnesium ion channel in prokaryotes and archaea. Synthetic antibodies (sABs) against CorA were generated using phage display selection strategies, and they showed different degrees of Mg2+-sensitivity. The sABs provided insights into the binding mode and mechanism of action of CorA.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sunbin Deng, Jiaxi Cai, Stephen C. Harrison, Huilin Zhou, Stephen M. Hinshaw
Summary: Successful mitosis relies on the correct attachment of chromosomes to microtubules. The kinetochore plays a crucial role in this process by recognizing specific chromatin and ensuring the formation of only one kinetochore per chromatid at the correct location. The crystal structure of the Cse4 peptide bound to the inner kinetochore Okp1-Ame1 complex provides insights into centromere recognition and the organization of the inner kinetochore.
Article
Multidisciplinary Sciences
Ulrike Leurs, Anders B. Klein, Ethan D. McSpadden, Nane Griem-Krey, Sara M. O. Solbak, Josh Houlton, Inge S. Villumsen, Stine B. Vogensen, Louise Hamborg, Stine J. Gauger, Line B. Palmelund, Anne Sofie G. Larsen, Mohamed A. Shehata, Christian D. Kelstrup, Jesper Olsen, Anders Bach, Robert O. Burnie, D. Steven Kerr, Emma K. Gowing, Selina M. W. Teurlings, Chris C. Chi, Christine L. Gee, Bente Frolund, Birgitte R. Kornum, Geeske M. van Woerden, Rasmus P. Clausen, John Kuriyan, Andrew N. Clarkson, Petrine Wellendorph
Summary: This study demonstrates the selective binding of compounds related to GHB to CaMKIIα, leading to increased thermal stability of the hub and providing neuroprotection, particularly under pathological conditions. This unexpected interaction establishes GHB analogs as powerful tools for investigating CaMKII neuropharmacology in general and as potential therapeutic compounds for cerebral ischemia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Dong Yun Lee, Yong-il Kim
Summary: This study conducted a meta-analysis on the therapeutic effects of Ac-225-PSMA RLT in patients with mCRPC. The results showed that around 61% of patients had more than a 50% PSA decline and 84% of patients had any PSA decline. The common adverse events in Ac-225-PSMA RLT were xerostomia and severe hematotoxicity.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Sven O. Dahms, Tanja Haider, Gerhard Klebe, Torsten Steinmetzer, Hans Brandstetter
Summary: The pro-protein convertase furin is an important enzyme that activates surface proteins of many viruses, including SARS-CoV-2. Inhibitors targeting furin can effectively suppress viral replication, showing broad application potential. Targeting furin in its OFF state can serve as a valuable strategy for structure-based development of PC-selective small-molecule inhibitors.
ACS CHEMICAL BIOLOGY
(2021)
Article
Engineering, Chemical
Indra Gandi Subramani, R. M. Ayub, Subash C. B. Gopinath, Veeradasan Perumal, M. F. M. Fathil, M. K. Md Arshad
Summary: The research introduces a novel approach using a lectin-based capacitive non-faradaic biosensor for detecting PSMA, a promising diagnostic marker for prostate cancer. The study demonstrates the potential of using PSMA expression to differentiate malignant hyperplasia from other benign prostatic diseases. By utilizing gold nanoparticles as signal amplifiers, the study successfully modified the aluminium interdigitated electrode to efficiently sense PSMA, showing a simple fabrication and quantification method for PSMA.
JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS
(2021)
Article
Chemistry, Multidisciplinary
Zheng Zhou, Jesus M. Fernandez-Garcia, Yikun Zhu, Paul J. Evans, Rafael Rodriguez, Jeanne Crassous, Zheng Wei, Israel Fernandez, Marina A. Petrukhina, Nazario Martin
Summary: Chemical reduction of pi-conjugated bilayer nanographene using K and Rb resulted in the formation of two new ion compounds, demonstrating an uncommon hydrogenation process in graphene that leads to changes and slippage in the bilayers. This provides a new insight into the structure and properties of graphene.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Physics, Applied
Jong Woo Kim, Mathew J. Cherukara, Ashish Tripathi, Zhang Jiang, Jin Wang
Summary: Coherent surface scattering imaging requires a mathematical conversion to visualize specimen structures, which can now be predicted using a deep learning neural network model to instantly obtain results from scattering patterns. This is highly beneficial for both experimental effectiveness and data analysis.
APPLIED PHYSICS LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Cen Chen, Ziyuan Fang, Zhen Huang
Summary: Crystallization phasing and obtaining high-quality crystals are major challenges for X-ray crystallographic analysis of nucleic acids. In this study, the authors addressed these challenges by incorporating selenium atoms into DNA duplexes, which resulted in larger and higher quality crystals compared to standard DNA crystals. These findings provide a simple strategy to overcome crystallization challenges in nucleic acid crystallography.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Biochemistry & Molecular Biology
Tiziano Marzo, Giarita Ferraro, Lorena Maria Cucci, Alessandro Pratesi, Orjan Hansson, Cristina Satriano, Antonello Merlino, Diego La Mendola
Summary: The study shows that the anti-cancer drug oxaliplatin efficiently binds angiogenin, inhibiting its promoting effects on cell proliferation and migration. This suggests angiogenin as a potential target of oxaliplatin, indicating a new mechanism for the anti-neoplastic activity of this platinum drug and opening avenues for novel approaches in combined anti-cancer anti-angiogenic therapy.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Microbiology
Jose A. Manso, Arturo Carabias, Zsuzsa Sarkany, Jose M. de Pereda, Pedro Jose Barbosa Pereira, Sandra Macedo-Ribeiro
Summary: The ability of Candida albicans to switch between yeast and hyphal forms is important for its pathogenicity, with CaRas1 playing a key role in this process. This study provides insights into the structure and activation of CaRas1, and identifies a synthetic peptide that can specifically inhibit its activation. These findings open up new possibilities for combating Candida albicans infections.
Article
Multidisciplinary Sciences
Akimitsu Higuchi, Wataru Shihoya, Masae Konno, Tatsuya Ikuta, Hideki Kandori, Keiichi Inoue, Osamu Nureki
Summary: SzRs, a newly identified rhodopsin family in Asgard archaea, exhibit unique kinetic behaviors in inward H+ release compared to other H+ pumps. The crystal structure of SzR AM_5_00977 revealed that key residues and structural features are different from other microbial rhodopsins, suggesting a distinct mechanism for inward H+ release.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Xinning Wang, Aditi Shirke, Ethan Walker, Rongcan Sun, Gopolakrishnan Ramamurthy, Jing Wang, Lingpeng Shan, Joey Mangadlao, Zhipeng Dong, Jing Li, Ziying Wang, Mark Schluchter, Dong Luo, Yu Wang, Shaun Stauffer, Susann Brady-Kalnay, Christopher Hoimes, Zhenghong Lee, James P. Basilion
Summary: Researchers have developed a new PSMA-targeting drug conjugate with potent and selective antitumor activity, showing potential to impact therapeutic management of lethal prostate cancers.
Article
Biology
Hai Li, Chia-Ying Huang, Elena G. Govorunova, Oleg A. Sineshchekov, Adrian Yi, Kenneth J. Rothschild, Meitian Wang, Lei Zheng, John L. Spudich
Summary: The crystal structure of bromide-bound GtACR1 reveals structural changes that relax the constrictions of the channel and involve a novel salt-bridge switch mechanism. These findings suggest that substrate binding induces a transition from an inactivated state to a pre-activated state in the dark, facilitating channel opening.
Review
Cell Biology
Jiaxian Chen, Lin Qi, Yongxiang Tang, Guyu Tang, Yu Gan, Yi Cai
Summary: PSMA-based PET imaging and RLT have promising roles in the diagnosis, treatment, and prediction of prognosis of CRPC. PSMA-based PET imaging accurately detects and monitors CRPC lesions, leading to optimal treatment selection. RLT is an effective and well-tolerated therapy that can be combined with PSMA imaging.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zora Novakova, Jana Mikesova, Marketa Ondrakova, Zsofia Kutil, Katerina Vesela, Pavel Martasek, Cyril Barinka
Summary: Variegate porphyria is caused by mutations in the PPOX gene, with the H333R mutation identified as a potential founder mutation in the Moroccan Jewish population. Experimental data shows that PPOX(H333R) lacks enzymatic activity in vitro, and molecular modeling suggests it fails to adopt its native functional three-dimensional conformation due to steric clashes. However, subcellular distribution of PPOX(H333R) is not affected, indicating the functional three-dimensional fold may not be necessary for efficient transport into mitochondria.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Wei Yuan, Baoqin Liu, Miloslav Sanda, Renhuizi Wei, Julius Benicky, Zora Novakova, Cyril Barinka, Radoslav Goldman
Summary: The study revealed differences in glycoforms of PSMA in various cells and tissues, which may lead to further research on tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
Article
Biochemistry & Molecular Biology
Shivam Shukla, Jan Komarek, Zora Novakova, Jana Nedvedova, Kseniya Ustinova, Pavla Vankova, Alan Kadek, Charlotte Uetrecht, Haydyn Mertens, Cyril Barinka
Summary: This study provides the first insights into the full-length structure of human HDAC6, showing that it is a mosaic of folded and intrinsically disordered domains and adopts an ensemble of conformations in solution. Furthermore, HDAC6 can form dimers/higher oligomers mediated by its positively charged N-terminal microtubule-binding domain.
Article
Multidisciplinary Sciences
Zora Novakova, Mirko Milosevic, Zsofia Kutil, Marketa Ondrakova, Barbora Havlinova, Petr Kasparek, Cristian Sandoval-Acuna, Zuzana Korandova, Jaroslav Truksa, Marek Vrbacky, Jakub Rohlena, Cyril Barinka
Summary: This study generated human cell lines with inactivated PPO using the CRISPR/Cas9 system and observed the accumulation of PPO substrate and reduced oxygen consumption, revealing the physiological consequences of dysregulated heme metabolism associated with variegate porphyria at the cellular level.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Jana Vondrakova, Michaela Frolikova, Lukas Ded, Jiri Cerny, Pavla Postlerova, Veronika Palenikova, Ondrej Simonik, Zuzana Nahacka, Krystof Basus, Eliska Valaskova, Radek Machan, Allan Pacey, Zuzana Holubcova, Pavel Koubek, Zuzana Ezrova, Soojin Park, Ruiwu Liu, Raghavendran Partha, Nathan Clark, Jiri Neuzil, Masahito Ikawa, Kent Erickson, Kit S. Lam, Harry Moore, Katerina Komrskova
Summary: This study identified a previously unidentified receptor, MAIA, which plays a major role in sperm-egg adhesion and fusion during mammalian fertilization. MAIA forms a stable interaction with the known IZUMO1/JUNO sperm-egg complex, allowing specific gamete fusion. The complexity of MAIA may provide a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes.
Article
Immunology
Veronika Daniel Liskova, Petr Kosztyu, Milan Kuchar, Jiri Cerny, Shiv Bharadwaj, Hana Petrokova, Eliska Vroblova, Michal Krupka, Michal Maly, Tereza Zosincukova, Josef Sulc, Leona Raskova Kafkova, Milan Raska, Petr Maly
Summary: The study demonstrates the potential of Myomedin-derived variants to mimic specific HIV-1 antibody epitopes, indicating promising candidates for HIV-1 vaccine development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vera Abramova, Vanessa Leal Alvarado, Martin Hill, Tereza Smejkalova, Michal Maly, Karel Vales, Ivan Dittert, Paulina Bozikova, Bohdan Kysilov, Barbora Hrcka Krausova, Vojtech Vyklicky, Ales Balik, Klevinda Fili, Miloslav Korinek, Hana Chodounska, Eva Kudova, David Ciz, Jan Martinovic, Jiri Cerny, Petr Bartunek, Ladislav Vyklicky
Summary: By investigating the major metabolites of the neuroprotective synthetic steroid PAG and their effects on GABAA and NMDA receptors, it was found that PAG and its metabolites are potent modulators of neurotransmitter receptors with behavioral consequences, indicating their potential therapeutic use.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matthes Zessin, Marat Meleshin, Sebastian Hilscher, Cordelia Schiene-Fischer, Cyril Barinka, Manfred Jung, Mike Schutkowski
Summary: Lysine deacetylases, including HDACs and SIRTs, are involved in various regulatory processes. SIRT2 and SIRT3 not only exhibit deacetylase activity but also demyristoylase activity. We introduced sirtuin substrates that allow direct fluorescence-based assays in a continuous format, enabling improved detection and determination of kinetic constants and inhibitor values.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Jakub Svoboda, Daniel Berdar, Petr Kolenko, Jiri Cerny, Zora NovaKova, Jiri Pavlicek, Bohdan Schneider
Summary: Nine new crystal structures of CG-rich DNA 18-mers related to bacterial repetitive extragenic palindromes are reported. Mutations of the central XZ dinucleotide in the 18-mers showed complex behavior in solution, but the successfully crystallized 18-mers were all A-form duplexes. The refinement protocol used the geometries of dinucleotide conformer classes as restraints and can be adapted to other low-resolution data.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lucia Motlova, Ivan Snajdr, Zsofia Kutil, Erik Andris, Jakub Ptacek, Adela Novotna, Zora Novakova, Barbora Havlinova, Werner Tueckmantel, Helena Draberova, Pavel Majer, Mike Schutkowski, Alan Kozikowski, Lubomir Rulisek, Cyril Barinka
Summary: This study reports on the synthesis and characterization of a series of oxadiazole-based inhibitors selectively targeting the HDAC6 isoform. Surprisingly, hydrolysis of the oxadiazole ring transforms it into an acylhydrazide, and the computed data support the proposed reaction mechanism.
ACS CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Bohdan Schneider, Blake Alexander Sweeney, Alex Bateman, Jiri Cerny, Tomasz Zok, Marta Szachniuk
Summary: Due to limited data and quality issues, it is challenging to predict the 3D structure of RNA using deep learning methods like AlphaFold in the short term. However, by addressing data quality and volume issues, utilizing more data, and developing new machine learning methods, an accurate RNA structure prediction method can be created.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Martin Maly, Petr Kolenko, Jan Stransky, Leona Svecova, Jarmila Duskova, Tomas Koval', Tereza Skalova, Maria Trundova, Kristyna Adamkova, Jiri Cerny, Paulina Bozikova, Jan Dohnalek
Summary: The resistance of Stenotrophomonas maltophilia to tetracycline antibiotics is mainly due to multidrug efflux pumps and ribosomal protection enzymes. However, some strains of this Gram-negative bacterium also possess a FAD-dependent monooxygenase (SmTetX), similar to tetracycline destructases. SmTetX was produced and studied, showing its ability to modify oxytetracycline. It shares a fold with TetX from Bacteroides thetaiotaomicron but has a unique aromatic region in its active site, and docking studies confirmed tetracycline and its analogues as preferred binders.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Gargi Das, Jakub Ptacek, Barbora Havlinova, Jana Nedvedova, Cyril Barinka, Zora Novakova
Summary: Prostate cancer is the leading cause of cancer-related deaths in men worldwide. Prostate-specific membrane antigen (PSMA) is currently the most prominent biomarker for prostate cancer and targeting PSMA has shown high efficacy in both imaging and therapy. Researchers have engineered and characterized a bispecific T-cell engager (BiTE) that enables host T lymphocytes to target PSMA-positive tumor cells. Their findings demonstrate the potential of the 5D3-alpha CD3 BiTE as an immuno-therapeutic modality for prostate cancer treatment.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)