Article
Chemistry, Physical
Sai Pooja Mahajan, Yashes Srinivasan, Jason W. Labonte, Matthew P. DeLisa, Jeffrey J. Gray
Summary: This study decoded the sequence and structural motifs determining peptide substrate preferences for the GalNAc-T2 isoform, revealing enzyme features that lead to finely tuned specificity for a broad range of peptide substrates. Computational scanning and experimental validation successfully discriminated glycosylatable peptides with high efficiency, providing insights for designing enzyme variants with tailored specificity in the future.
Review
Immunology
Erik P. Lillehoj, Irina G. Luzina, Sergei P. Atamas
Summary: Mammalian neuraminidases (NEUs) have metabolic functions and also regulate the activity of glycoproteins. They modify protein folding, interactions, and proteolytic sites by removing sialic acid. Desialylation of mucins (MUCs) by NEUs contributes to disease regulation. NEU1 and MUC1 play important roles in disease pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angelica Zamudio-Ochoa, Yaroslav Morozov, Azadeh Sarfallah, Michael Anikin, Dmitry Temiakov
Summary: Recognition of mammalian mitochondrial promoters is achieved through the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. This study provides insights into the heterogeneity of mitochondrial transcripts and accurately identifies the transcription start sites (TSS) of mammalian and other vertebrate species. The divergent structure of mammalian promoters reveals new aspects of mtDNA evolution and the precise register of the DNA in the initiation complex. The findings also shed light on the molecular basis of promoter recognition and the role of mitochondrial transcription machinery in mitonuclear coevolution and speciation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
David Zapletal, Eliska Taborska, Josef Pasulka, Radek Malik, Karel Kubicek, Martina Zanova, Christian Much, Marek Sebesta, Valeria Buccheri, Filip Horvat, Irena Jenickova, Michaela Prochazkova, Jan Prochazka, Matyas Pinkas, Jiri Novacek, Diego F. Joseph, Radislav Sedlacek, Carrie Bernecky, Donal O'Carroll, Richard Stefl, Petr Svoboda
Summary: The DExD/H domain of Dicer plays a crucial structural role in mammalian miRNA biogenesis. It locks Dicer in a closed state, facilitating miRNA precursor selection. Absence or mutations of the DExD/H domain unlock Dicer and activate RNAi.
Article
Biochemistry & Molecular Biology
Natalia Stach, Abdulkarim Karim, Przemyslaw Golik, Radoslaw Kitel, Katarzyna Pustelny, Natalia Gruba, Katarzyna Groborz, Urszula Jankowska, Sylwia Kedracka-Krok, Benedykt Wladyka, Marcin Drag, Adam Lesner, Grzegorz Dubin
Summary: By studying the substrate specificity and structure of SplF, it was found that the enzyme has a strict preference for long aliphatic sidechains at the P1 subsite and significant selectivity for aromatic residues at P3, with its crystal structure defining the structural basis of this substrate specificity. Comparisons with other Spl proteases suggest that the spl operon encodes a unique extracellular proteolytic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gyanendra Kumar, Maxime Cuypers, Richard R. Webby, Thomas R. Webb, Stephen W. White
Summary: The endonuclease activity within the influenza virus cap-snatching process is a proven therapeutic target. Baloxavir, an anti-influenza drug, is effective but linked to resistance mutations. By studying complexes of PA(N) with RNA and DNA oligonucleotides, insights are gained on specificity and structural basis of baloxavir resistance mutations.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biology
Dominik Layer, Juergen Kopp, Miriam Fontanillo, Maja Koehn, Karine Lapouge, Irmgard Sinning
Summary: Layer et al. present a crystal structure of Naa20, the catalytic subunit of an N-terminal acetyltransferase NatB, in complex with its competitive inhibitor CoA-Ac-MDEL. They find that Naa20 alone can acetylate NatB in vitro while Naa25, the auxiliary subunit of Naa20, increases the substrate affinity of Naa20. This study provides insights into the development of NAT inhibitors.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Atsushi Okawa, Tomoo Shiba, Masaya Hayashi, Yuki Onoue, Masaki Murota, Dan Sato, Junko Inagaki, Takashi Tamura, Shigeharu Harada, Kenji Inagaki
Summary: The crystal structures of L-Methionine decarboxylase revealed key residues determining substrate specificity and confirmed the role of crucial residues in enzyme reaction intermediates. The study provides important insights into the catalytic mechanism of MetDC.
Article
Biochemistry & Molecular Biology
Chen Wang, Qingjie Xiao, Huaichuan Duan, Jinhong Li, Jiying Zhang, Qisheng Wang, Li Guo, Jianping Hu, Bo Sun, Dong Deng
Summary: Nucleoside homeostasis mediated by transporters and channels is essential for life, and NupG in Escherichia coli serves as a prototype for nucleoside transport. The crystal structures of NupG and its uridine binding site provide a framework for understanding the mechanism of nucleoside transporters in the NHS family.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Robbins Puthenveetil, Shelby A. Auger, Natalia Gomez-Navarro, Mitra Shumsher Rana, Riki Das, Liam Brendan Healy, Kiall F. Suazo, Zhen-Dan Shi, Rolf E. Swenson, Mark D. Distefano, Anirban Banerjee
Summary: Protein palmitoylation is the most prevalent form of protein lipidation and is involved in various cellular processes and human diseases. There is currently no global strategy to identify physiological substrates of individual zDHHC enzymes. This study outlines a general approach using synthetic orthogonal substrates to accomplish this task.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Jialiang Wang, Jingdan Liang, Lu Chen, Wei Zhang, Liangliang Kong, Chao Peng, Chen Su, Yi Tang, Zixin Deng, Zhijun Wang
Summary: Statins, effective cholesterol-lowering drugs, depend on a megasynthase complex for biosynthesis. CryoEM structures of LovB-LovC and core LovB provide insights into the catalytic cycle for lovastatin production.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Laura Klenow, Rageia Elfageih, Jin Gao, Hongquan Wan, Stephen G. Withers, Jan-Willem de Gier, Robert Daniels
Summary: Influenza A viruses and pneumococci both express neuraminidases that catalyze release of sialic acid residues. The enzymatic properties of neuraminidases from both pathogens were compared, and it was found that they have evolved similar yet distinct strategies to optimize their catalytic activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Elizabeth M. Corteselli, Mona Sharafi, Robert Hondal, Maximilian MacPherson, Sheryl White, Ying-Wai Lam, Clarissa Gold, Allison M. Manuel, Albert van der Vliet, Severin T. Schneebeli, Vikas Anathy, Jianing Li, Yvonne M. W. Janssen-Heininger
Summary: This study provides insights into the mechanisms of oxidative inactivation of GLRX through molecular modeling and biochemical validation. The study identifies C8 and C83 as target sites for S-glutathionylation and oxidation, with C8 playing a prominent role in dimer formation and aggregation. Combinatorial mutation of C8, C26, and C83 results in increased activity of GLRX and resistance to oxidative inactivation and aggregation.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
David B. Sauer, Jennifer J. Marden, Joseph C. Sudar, Jinmei Song, Christopher Mulligan, Da-Neng Wang
Summary: In this study, the authors demonstrate that the VcINDY protein couples sodium and substrate binding through a cooperative mechanism by conformational selection. The results provide strong evidence for the sodium-dependent formation of the substrate binding site.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Yeongjin Yun, Sangjun Han, Yoon Sik Park, Hyunjae Park, Dogyeong Kim, Yeseul Kim, Yongdae Kwon, Sumin Kim, Jung Hun Lee, Jeong Ho Jeon, Sang Hee Lee, Lin-Woo Kang
Summary: Metallo-beta-lactamases (MBLs) plays a crucial role in the hydrolysis of antibiotics. However, effective clinical inhibitors for MBLs are currently unavailable. This study systematically investigated the primary sequences and crystal structures of MBLs, focusing on the conserved scaffold, zinc-coordinating residues, and substrate-binding pocket. The comparison among MBL subclasses revealed structural differences and highlighted the importance of the substrate-binding pocket in substrate specificity and drug resistance. The findings provide valuable insights for the development of clinical inhibitors targeting MBLs.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Amgad Albohy, Eman Maher Zahran, Usama Ramadan Abdelmohsen, M. Alaraby Salem, Tarfah Al-Warhi, Mohammad M. Al-Sanea, Narek Abelyan, Hany Ezzat Khalil, Samar Yehia Desoukey, Mostafa Ahmed Fouad, Mohamed Salah Kamel
Summary: This article explores the potential of compounds derived from plants in combating the novel coronavirus. By analyzing the metabolomics and using chromatographic techniques, 14 compounds were identified and their binding interactions with viral targets were studied through molecular docking. The study reveals that three of these compounds have strong binding affinities and could potentially be used as antiviral drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Md Amran Howlader, Ekaterina P. Demina, Suzanne Samarani, Tianlin Guo, Antoine Caillon, Ali Ahmad, Alexey Pshezhetsky, Christopher W. Cairo
Summary: The isoenzymes of the neuraminidase family (NEU1, 3, and 4) play essential roles in the activation, extravasation, and migration of immune cells in the induction of acute inflammatory response. NEU1 and NEU3 deficiency decreases leukocyte recruitment, while NEU4 deficiency increases it, indicating opposite effects of NEU isoenzymes on leukocyte infiltration. Further investigation is needed to determine the mechanisms and importance of NEU isoenzymes as regulators of the inflammatory cascade.
Article
Chemistry, Medicinal
Tarfah Al-Warhi, Ahmed M. El Kerdawy, Mohamed A. Said, Amgad Albohy, Zainab M. Elsayed, Nada Aljaeed, Eslam B. Elkaeed, Wagdy M. Eldehna, Hatem A. Abdel-Aziz, Miral A. Abdelmoaz
Summary: In this study, various thiazolyl-pyrazoline derivatives were synthesized and evaluated for their anti-tumor activities. Compounds 7g and 7m showed the best activity against both lung cancer and breast cancer cells, with potential for EGFR inhibition.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Ibrahim S. Uras, Michal Korinek, Amgad Albohy, Basma S. Abdulrazik, Wenhan Lin, Sherif S. Ebada, Belma Konuklugil
Summary: In this study, the potential therapeutic effects of compounds isolated from a marine-derived fungus extract were investigated through experiments on inflammation, allergy, and viral enzyme activity, revealing that two butenolide derivatives showed potential for treatment.
Article
Pharmacology & Pharmacy
Rana E. Kamal, Esther Menze, Amgad Albohy, Hebatalla I. Ahmed, Samar S. Azab
Summary: This study evaluated the potential of carvedilol as an anti-Parkinson's drug and anti-tau protein target through computational simulation and in vivo experiments. The results suggest that carvedilol has neuro-protective effects and may be a candidate for the management of Parkinson's disease.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nourhan Hisham Shady, Hend Samy Abdullah, Sherif A. Maher, Amgad Albohy, Mahmoud A. Elrehany, Fatma Alzahraa Mokhtar, Hesham Farouk Oraby, Ahmed M. Shawky, Usama Ramadan Abdelmohsen
Summary: The present study aimed to explore the gastroprotective effect of Psidium guajava seeds extract (PGE). It was found that PGE significantly decreased the ulcer index and protected the mucosa from lesions. Additionally, PGE reduced inflammatory reactions, promoted ulcer healing, and exhibited high antioxidant potential. This study provided evidence for the potential use of Psidium guajava seeds as a natural gastroprotective agent.
Article
Chemistry, Multidisciplinary
Ihab Shawish, Assem Barakat, Ali Aldalbahi, Azizah M. Malebari, Mohamed S. Nafie, Adnan A. Bekhit, Amgad Albohy, Alamgir Khan, Zaheer Ul-Haq, Matti Haukka, Beatriz G. de la Torre, Fernando Albericio, Ayman El-Faham
Summary: In this study, a series of novel 1,3,5-triazine derivatives were synthesized and their inhibitory activity against cancer cells was evaluated through in vitro assays. Among them, compound 4f showed significant antitumor activity and induced apoptosis by targeting EGFR and its downstream pathway.
Article
Chemistry, Medicinal
Refaie M. Kassab, Sami A. Al-Hussain, Nooran S. Elleboudy, Amgad Albohy, Magdi E. A. Zaki, Khaled A. M. Abouzid, Zeinab A. Muhammad
Summary: This study designed and synthesized novel isatin-decorated thiazole derivatives that exhibited strong antimicrobial and antifungal activities, potentially targeting TyrRS. These compounds showed antimicrobial activity against gram-negative bacteria and Methicillin Resistant Staphylococcus aureus (MRSA), as well as antifungal activity against Candida albicans and biofilm formation inhibition.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Mousa AlTarabeen, Qosay Al-Balas, Amgad Albohy, Werner Ernst Georg Mueller, Peter Proksch
Summary: Manzamines are a group of compounds extracted from Acanthostrongylophora ingens species. We have identified and characterized seven compounds. Based on previous screening work by Mayer et al., who suggested that manzamine A could be an inhibitor of RSK1 kinase, our work focused on targeting the RSK1 N-terminal kinase domain. Docking using Autodock Vina software showed that Manzamine A N-oxide (5) exhibited the highest activity with an IC50 value of 3.1 μM.
Article
Biology
Murtaza S. Nagree, Jitka Rybova, Annie Kleynerman, Carissa J. Ahrenhoerster, Jennifer T. Saville, TianMeng Xu, Maxwell Bachochin, William M. McKillop, Michael W. Lawlor, Alexey V. Pshezhetsky, Olena Isaeva, Matthew D. Budde, Maria Fuller, Jeffrey A. Medin
Summary: Mutations in the ASAH1 gene are associated with two distinct disorders, Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). This study describes a mouse model with an SMA-PME-like phenotype (P361R-SMA) caused by a specific mutation in the ASAH1 gene. The P361R-SMA mice show progressive ataxia, bladder dysfunction, demyelination, loss of axons, and altered sphingolipid levels in the spinal cords, providing a valuable tool for studying the effects of ASAH1 deficiency and evaluating potential therapies for SMA-PME.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lorena Carvelli, Louis Hermo, Cristian O'Flaherty, Richard Oko, Alexey V. Pshezhetsky, Carlos R. Morales
Summary: The inactivation of Hgsnat resulted in morphological alterations in the testis, affecting the area of seminiferous tubules and the epithelial profile. Abnormalities in Sertoli cells, blood-testis barrier, and sperm morphology were observed. In the epididymis, there were significant accumulations of lysosomes and morphological changes in the epithelial cells.
Article
Medicine, Research & Experimental
Ikhui Kho, Ekaterina P. Demina, Xuefang Pan, Irene Londono, Christopher W. Cairo, Luisa Sturiale, Angelo Palmigiano, Angela Messina, Domenico Garozzo, Roth-Visal Ung, Fabrice Mac-Way, Eric Bonneil, Pierre Thibault, Mathieu Lemaire, Carlos R. Morales, Alexey V. Pshezhetsky
Summary: Sialidosis is an ultra-rare lysosomal disease caused by mutations in the NEU1 gene. Deficiency of NEU1 impairs protein reabsorption and contributes to the development of glomerular nephropathy and kidney damage.
Article
Biology
M. Mojally, R. Abdou, W. Bokhari, S. Sab, M. Dawoud, A. Albohy
Summary: Secondary metabolites produced by endophytes are valuable sources of biologically active compounds. The newly discovered natural products terezine E and 14-hydroxyterezine D exhibited anti-cancer activity in our study, and their affinity for binding to specific enzymes was evaluated using molecular docking. Furthermore, their cytotoxicity, antimicrobial activity, and minimum inhibitory concentration values were assessed. Terezine E showed higher cytotoxicity and antimicrobial activity than 14-hydroxyrerezine D.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Amr Adel, Mohamed S. Elnaggar, Amgad Albohy, Ahmed A. Elrashedy, Ahmed Mostafa, Omnia Kutkat, Usama Ramadan Abdelmohsen, Eman Al-Sayed, Mohamed A. Rabeh
Summary: This study evaluated the anti-SARS-CoV-2 activity of extracts from Carica papaya leaves cultivated in Egypt and found that the n-hexane fraction exhibited high antiviral activity. Analysis of the crude extract revealed the presence of various compounds known to possess antiviral activity against different classes of viruses. Computational simulations also showed promising interactions between the annotated compounds and SARS-CoV-2 target proteins.
Article
Chemistry, Multidisciplinary
Mohamed A. Said, Amgad Albohy, Mohamed A. Abdelrahman, Hany S. Ibarhim
Summary: In this study, researchers utilized drug databases and virtual screening analysis to identify a promising candidate drug, remdesivir, against SARS-CoV-2. They also designed analogs HA-130383 and HA-130384 based on scaffold replacement and structure-based pharmacophore. These analogs showed potential as lead compounds.