Article
Biochemistry & Molecular Biology
Natalia Zamorano Cuervo, Nathalie Grandvaux
Summary: Protein disulfide isomerases (PDIs) are enzymes that catalyze redox reactions and have chaperone functions in protein folding. PDIs have catalytic thioredoxin (TRX)-like domains with CXXC motifs for redox reactions, as well as non-catalytic TRX-like domains. Strategies for identifying cysteine oxidative post-translational modifications (Cys ox-PTMs) have been optimized, and analysis of a Cys redoxome dataset suggests the presence of a non-catalytic thiol-disulfide motif in PDIs. Further structural analysis and exploration of other PDIs are needed to understand the role of these motifs.
Article
Biochemistry & Molecular Biology
Mirva J. Saaranen, Heli Alanen, Kirsi E. H. Salo, Emmanuel Nji, Pekka Karkkainen, Constanze Schmotz, Lloyd W. Ruddock
Summary: Proteins in the thioredoxin superfamily, such as protein disulfide isomerase (PDI) and glutaredoxins, have similar structures and catalytic mechanisms. PDI uses glutathione for oxidation/reduction in vitro, while glutaredoxins have a high affinity for glutathione. Mutating the active site of PDI to a more glutaredoxin-like motif increases its reactivity with glutathione.
Article
Biochemistry & Molecular Biology
Mariana H. Moreira, Fabio C. L. Almeida, Tatiana Domitrovic, Fernando L. Palhano
Summary: Defensins are small, amphipathic proteins with disulfide bonds, challenging tertiary protein structure predictors. Comparing defensins with non-defensins showed no differences in residue proportions and solvent exposure. Bonded small proteins had more exposed apolar residues than unbonded proteins, with Robetta predicting unbonded proteins more accurately. trRosetta, using AI, improved prediction for bonded proteins but not unbonded ones, highlighting the complexity of predicting protein tertiary structures.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Carlos Santos-Martin, Geqing Wang, Pramod Subedi, Lilian Hor, Makrina Totsika, Jason John Paxman, Begona Heras
Summary: The DsbA enzyme, as part of the disulfide bond forming system, plays a crucial role in bacterial virulence factor assembly and is a potential target for new virulence blockers. Despite extensive studies on DSB systems in various bacterial species, little is known about how DsbA oxidoreductases recognize and interact with a wide range of substrates.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Maho Yagi-Utsumi, Haruko Miura, Christian Ganser, Hiroki Watanabe, Methanee Hiranyakorn, Tadashi Satoh, Takayuki Uchihashi, Koichi Kato, Kei-ichi Okazaki, Kazuhiro Aoki
Summary: This study utilized the dynamic properties of multidomain proteins to develop a novel FRET-based biosensor by fusing b' and a' domains with fluorescent proteins. The biosensor demonstrated higher FRET efficiency in the oxidized form and has potential applications in studying cellular redox regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Xulin Xu, Joyce Chiu, Shuai Chen, Chao Fang
Summary: PDI, a prototypic member of the thiol isomerase family, plays crucial roles not only in the endoplasmic reticulum but also on the cell surface and in the extracellular matrix. The in-depth study of the pathophysiological roles and molecular mechanisms of surface and extracellular PDI contributes to a better understanding of the molecular etiology of diseases.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Mary E. Law, Elham Yaaghubi, Amanda F. Ghilardi, Bradley J. Davis, Renan B. Ferreira, Jin Koh, Sixue Chen, Sadie F. DePeter, Christopher M. Schilson, Chi-Wu Chiang, Coy D. Heldermon, Peter Norgaard, Ronald K. Castellano, Brian K. Law
Summary: Breast cancer mortality remains high, and there is a need for safer and more effective treatments. Disulfide bond Disrupting Agents (DDAs) have been identified as a potential class of anticancer compounds that specifically target EGFR and HER2 overexpressing cancer cells. The study found that DDAs act by downregulating EGFR, HER2, and HER3 and activating Death Receptors 4 and 5 (DR4/5). Further analysis revealed that AGR2, PDIA1, and ERp44 are the target proteins of DDAs. DDAs disrupt the mixed disulfide bonds between PDIA1, ERp44, and their client proteins, and enhance basal DR5 oligomerization by targeting AGR2 and ERp44.
Article
Biochemistry & Molecular Biology
Yoshiyuki Matsuo
Summary: The presence of a large number of thioredoxin superfamily members indicates a complex redox-based regulation mechanism in mammalian cells. Thioredoxin-like proteins are found in the endoplasmic reticulum, with a specific family of TMX proteins residing in the ER membrane and playing crucial roles in cellular processes. Further research is needed to understand the physiological roles of TMX family proteins and how they can be targeted for drug discovery in various human diseases.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biology
Motonori Matsusaki, Rina Okada, Yuya Tanikawa, Shingo Kanemura, Dai Ito, Yuxi Lin, Mai Watabe, Hiroshi Yamaguchi, Tomohide Saio, Young-Ho Lee, Kenji Inaba, Masaki Okumura
Summary: The physiological functions of proteins are determined by their unique three-dimensional structures, with conserved disulfide-catalysts and chaperone networks playing a crucial role in correct protein folding and prevention of aggregation. Disruption of these networks is implicated in pathology. Complex formation among PDIs accelerates protein folding and prevents aggregation.
Review
Oncology
Suhui Yang, Chanel Jackson, Eduard Karapetyan, Pranabananda Dutta, Dulcie Kermah, Yong Wu, Yanyuan Wu, John Schloss, Jaydutt V. Vadgama
Summary: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, while protein disulfide isomerase (PDI) has been identified as a potential therapeutic target due to its role in tumor progression. Selective blockade of PDI can induce apoptosis through sustained activation of UPR pathways. Future research should focus on the roles of PDI in highly metastatic breast cancers like TNBC.
Article
Biochemistry & Molecular Biology
Pingyu Yan, Zhiyuan Zou, Shiyao Zhang, Rui Wang, Tingting Niu, Xia Zhang, Defu Liu, Xuejie Zhou, Alan K. Chang, Nathaniel G. N. Milton, Gary W. Jones, Jianwei He
Summary: The study investigated the binding between Pichia pastoris PDI and amyloidogenic proteins, revealing multiple binding modes between PDI and its substrates, suggesting different specificities and affinities. PDI may eliminate the need for misfolded proteins to be localized in ER-associated compartments by promoting protein folding.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Yayoi Onda, Tomoya Okino
Summary: This study highlights the crucial role of thiol-disulfide oxidoreductase PDI1;1 in actin structures. PDI1;1 can recognize and degrade the disulfide bonds in high-molecular-weight structures of actin.
Article
Nanoscience & Nanotechnology
Danping Wang, Chaoying Du, Shuo Wang, Lingxiao Li, Tian Liu, Jiaxuan Song, Zhonggui He, Yinglei Zhai, Bingjun Sun, Jin Sun
Summary: The connecting bonds and modifying chains play a vital role in the rational design of prodrug nanoassemblies and have significant impact on their characteristics and anticancer effects.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Manuela Florido, Joyce Chiu, Philip J. Hogg
Summary: The research indicates that the disulfide bonds in the HA protein of influenza A virus are in high-energy conformations and potentially labile. These bonds are impervious to thiol isomerases when expressed on the viral surface.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Virology
Huanyu Zhang, Wenhua Kuang, Congcong Fu, Jiang Li, Manli Wang, Zhihong Hu
Summary: The study identified that the baculovirus core gene ac81 likely encodes a disulfide isomerase which plays a crucial role in various functions of the baculovirus life cycle. This suggests that viral disulfide bond formation could be an ancient mechanism shared by insect-specific large DNA viruses like baculoviruses, nudiviruses, and hytrosaviruses encoding AC81 and P33 (sulfhydryl oxidase).
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marian Vincenzi, Flavia Anna Mercurio, Concetta Di Natale, Rosanna Palumbo, Luciano Pirone, Sara La Manna, Daniela Marasco, Emilia Maria Pedone, Marilisa Leone
Summary: This study describes the design and functional evaluation of KRI3 analogues that bind to Ship2-Sam. The importance of aromatic interactions for the association with Ship2-Sam is highlighted. Additionally, preliminary cell-based assays demonstrate the cellular uptake capability of KRI3.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sonia Di Gaetano, Luciano Pirone, Ioannis Galdadas, Serena Traboni, Alfonso Iadonisi, Emilia Pedone, Michele Saviano, Francesco Luigi Gervasio, Domenica Capasso
Summary: Galectins are soluble proteins involved in cancer progression and disease outcome, making them important targets for therapeutic intervention. Developing small inhibitors to selectively block galectin activity is a promising strategy for cancer therapy. This study designed a novel compound with high binding affinity to galectins and demonstrated its potential anticancer properties, paving the way for further development as an anticancer agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Luis Exequiel Ibarra, Simona Camorani, Lisa Agnello, Emilia Pedone, Luciano Pirone, Carlos Alberto Chesta, Rodrigo Emiliano Palacios, Monica Fedele, Laura Cerchia
Summary: Photodynamic therapy (PDT) may be a promising alternative for the treatment of breast cancer, especially for aggressive types like triple-negative breast cancer (TNBC). A recent study explored the use of conjugated polymer nanoparticles (CPNs) as photosensitizers for targeted PDT. By attaching unique 2'-Fluoropyrimidines-RNA-aptamers to the surface of CPNs, the researchers aimed to improve the selectivity of the treatment for TNBC cells. Results showed that CL4, sTN29, and sTN58 aptamers were effective in selective tumor targeting and improving PDT efficacy in TNBC cells.
Review
Biochemistry & Molecular Biology
Fabiana Cacace, Rossella Iula, Danilo De Novellis, Valeria Caprioli, Maria Rosaria D'Amico, Giuseppina De Simone, Rosanna Cuccurullo, William G. Wierda, Kris Michael Mahadeo, Giuseppe Menna, Francesco Paolo Tambaro
Summary: Pediatric acute myeloid leukemia is a clonal disorder characterized by malignant transformation of the hematopoietic stem cell. Treatment includes chemotherapy and stem cell transplantation. Although prognosis has improved, it remains inferior to pediatric acute lymphoblastic leukemia.
Review
Biochemistry & Molecular Biology
Emma Langella, Anna Di Fiore, Vincenzo Alterio, Simona Maria Monti, Giuseppina De Simone, Katia D'Ambrosio
Summary: This article provides an overview of recent literature on alpha-CAs from photosynthetic organisms, discussing their functions and mechanisms in higher plants, algae, and cyanobacteria. It emphasizes the need for further research to understand the structure-function relationship of alpha-CAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Hematology
Fabiana Cacace, Selenia Vitiello, Franceso Muriano, Daniela D'Angelo, Valeria Caprioli, Maria Rosaria D'Amico, Giuseppina De Simone, Rosanna Parasole, Francesco Paolo Paolo Tambaro
Meeting Abstract
Hematology
Daniela D'Angelo, Fabiana Cacace, Valeria Caprioli, Maria Rosaria D'Amico, Giuseppina De Simone, Roberta Penta, Mario Toriello, Giovanna Maisto, Stefania Nappo, Francesco Paolo Paolo Tambaro
Article
Cell Biology
Annachiara Sarnella, Ylenia Ferrara, Sandra Albanese, Daniela Omodei, Laura Cerchia, Giuseppina De Simone, Claudiu T. Supuran, Antonella Zannetti
Summary: Conventional chemotherapy is the main treatment for TNBC patients, but drug resistance is common. This study showed that BM-MSCs and CA IX play a role in reducing cisplatin sensitivity in TNBC. Inhibiting CM-MSC-induced CA IX using SLC-0111 enhanced chemotherapy efficacy and inhibited TNBC cell migration and invasion.
Article
Chemistry, Medicinal
Alessio Nocentini, Alessandro Bonardi, Carla Bazzicalupi, Vincenzo Alterio, Davide Esposito, Simona Maria Monti, Michael Smietana, Giuseppina De Simone, Claudiu T. Supuran, Paola Gratteri, Jean-Yves Winum
Summary: In this study, substituted 6-(1H-1,2,3-triazol-1-yl)benzoxaboroles were synthesized and characterized using in silico design. The 6-azidobenzoxaborole was introduced as a molecular platform for preparing libraries of inhibitors through a click chemistry strategy. Compound 20 showed high selectivity as hCAVII and IX inhibitors with inhibition constants below 30 nM. Crystallographic investigation validated the design hypothesis and provided explanations for the different inhibition behavior observed against five hCA isoforms. Overall, compound 20 was identified as a promising lead compound to develop novel anticancer agents targeting hCA IX and potent neuropathic pain relievers targeting hCA VII.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Emma Langella, Davide Esposito, Simona Maria Monti, Claudiu T. Supuran, Giuseppina De Simone, Vincenzo Alterio
Summary: Carbonic anhydrases are enzymes involved in an important physiological reaction of converting CO2 to bicarbonate ion. They play crucial roles in various physiological and pathological processes in humans, making them potential targets for therapeutic interventions. This study investigates a class of carbonic anhydrase inhibitors, providing insights into their mechanism of action and potential for drug design.
Article
Multidisciplinary Sciences
Mariangela Succoio, Sara Amiranda, Emanuele Sasso, Carmen Marciano, Arianna Finizio, Giuseppina De Simone, Corrado Garbi, Nicola Zambrano
Summary: The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein involved in pH regulation in hypoxic cells. It is frequently expressed in cancer cells and contributes to tumor progression. This study aimed to understand the mechanisms of CA IX subcellular distribution by targeting the C-terminal domain of CA IX through site-directed mutagenesis in the SH-SY5Y cell line. The results suggest that CA IX nuclear translocation depends on its transit through the secretory and endocytic pathways.
Meeting Abstract
Oncology
Annachiara Sarnella, Ylenia Ferrara, Luigi Auletta, Sandra Albanese, Vincenzo Alterio, Jean-Yves Winum, Claudiu T. Supuran, Laura Cerchia, Giuseppina De Simone, Antonella Zannetti
Article
Biochemistry & Molecular Biology
Carmine Marco Morgillo, Antonio Lupia, Alessandro Deplano, Luciano Pirone, Bianca Fiorillo, Emilia Pedone, F. Javier Luque, Valentina Onnis, Federica Moraca, Bruno Catalanotti
Summary: FAAH is a key enzyme in controlling cannabinoid signaling, and research on the mechanism of action of the non-competitive inhibitor TPA14 has provided a theoretical basis for the design of effective drugs for the treatment of neuropathic pain and chronic inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anna Di Fiore, Viviana De Luca, Emma Langella, Alessio Nocentini, Martina Buonanno, Simona Maria Monti, Claudiu T. Supuran, Clemente Capasso, Giuseppina De Simone
Summary: This paper presents a detailed characterization of BpsyCA, a y-carbonic anhydrase from Burkholderia pseudomallei, highlighting its catalytic activity, crystal structure, and the role of residues in its catalytic mechanism and ligand recognition. These findings provide an important starting point for the development of new anti-melioidosis drugs targeting BpsyCA.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
Summary: This review summarizes existing literature data on the post-translational modifications of hCA IX and hCA XII, emphasizing their specific role in cancer pathological processes. Limited data are currently available on these modifications and their functional implication in the tumor environment.
