Article
Food Science & Technology
Ekaterina N. N. Lyukmanova, Pavel A. A. Mironov, Dmitrii S. S. Kulbatskii, Mikhail A. A. Shulepko, Alexander S. S. Paramonov, Elizaveta M. M. Chernaya, Yulia A. A. Logashina, Yaroslav A. A. Andreev, Mikhail P. P. Kirpichnikov, Zakhar O. O. Shenkarev
Summary: This article reports on the neurotoxin Phα1β (PnTx3-6) from the venom of the spider Phoneutria nigriventer, which acts as an antagonist on two ion channels involved in nociception. The study demonstrates that Phα1β can reduce both acute and chronic pain. NMR spectroscopy was used to determine the spatial structure and dynamics of Phα1β, providing important insights into the structure and function of spider toxins.
Article
Chemistry, Physical
Fengyi Cao, Gangqing Ma, Lin Mei, Genxing Zhu, Meng Song, Qi Qin, Mingli Jiao
Summary: In this study, a cysteine-containing PAF26 peptide derivative was designed to develop a covalently crosslinked antimicrobial hydrogel, which showed strong crosslinked networks and excellent antimicrobial abilities against Candida albicans, Staphylococcus aureus, and Escherichia coli.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2021)
Article
Biochemistry & Molecular Biology
Junko Tanaka, Satoshi Abe, Tohru Hayakawa, Mariko Kojima, Keitaro Yamashita, Kunio Hirata, Takafumi Ueno
Summary: In-cell protein crystals that spontaneously crystallize in living cells have been analyzed to understand their structures and biological functions. However, their small size has made it challenging to determine their structures. In this study, the cross-linked network of disulfide bonds within Cry1Aa crystals, a cysteine-rich protein that crystallizes in Bacillus thuringiensis, was characterized through direct X-ray crystallographic analysis using crystals purified from Bt cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
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)
Article
Chemistry, Multidisciplinary
Huanyu Tao, Qilong Wu, Xuejun Zhao, Peicong Lin, Sheng-You Huang
Summary: MODPEP2.0 is an efficient tool for sampling cyclic peptide structures, which can quickly generate conformations of cyclic peptides with considerable accuracy and computational efficiency compared to other sampling algorithms.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Chemistry, Applied
Sindija Lapcinska, Pavels Dimitrijevs, Pavel Arsenyan
Summary: A visible light-initiated method has been developed for the preparation of Se-S bond-containing peptides, showing good tolerance, stability, and the ability to serve as an oxidation-sensitive linker.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Materials Science, Multidisciplinary
Na Li, Ying Ma, Niuniu Chen, Xiaoyu Tang, Shanshan Lv
Summary: This study investigates the effect of microwave on the stability of peptide bonds in silk protein, and finds that microwave irradiation causes minor damage and negligible cleavage of the peptide bonds compared to conventional heating methods, making it suitable for silk protein dissolution.
ADVANCED FIBER MATERIALS
(2022)
Article
Chemistry, Organic
Ma Yannan, Liu Ya'ni, Wang Jinyan, Chen Xitong, Yin Hao, Chi Qiaona, Jia Shixi, Du Shanshan, Qi Yunkun, Wang Kewei
Summary: The efficiency and robustness of the DIC/Oxyma condensation system were evaluated for the synthesis of GsMTx4 peptide, resulting in the successful and active production of GsMTx4.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Melissa E. Reardon-Robinson, Minh Tan Nguyen, Belkys C. Sanchez, Jerzy Osipiuk, Christian Ruckert, Chungyu Chang, Bo Chen, Rahul Nagvekar, Andrzej Joachimiak, Andreas Tauch, Asis Das, Hung Ton-That
Summary: In many gram-positive Actinobacteria, MdbA plays a crucial role in bacterial viability by catalyzing oxidative folding of exported proteins. However, in Corynebacterium diphtheriae, the deletion of mdbA only affects cell growth at 37°C, suggesting the existence of alternative oxidoreductase enzymes. Through genetic suppressor mutations, we discovered that elevated expression of tsdA can compensate for the loss of mdbA by mediating oxidative folding of pilin and toxin substrates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Pharmacology & Pharmacy
Taylor B. Smallwood, Richard J. Clark
Summary: Animal venoms are complex mixtures of bioactive molecules, with disulfide-rich peptides being a major component. The study of venom-derived drugs has led to advancements in treating diseases such as type 2 diabetes and chronic pain. New techniques are expanding the pipeline of venom-derived peptides, offering potential for therapeutic applications and increased understanding of molecular targets.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Donatella Diana, Rossella Di Stasi, Sara Garcia-Vinuales, Lucia De Rosa, Carla Isernia, Gaetano Malgieri, Danilo Milardi, Luca D. D'Andrea, Roberto Fattorusso
Summary: Thermal unfolding studies provide a useful tool for understanding the conformational transitions in protein folding, with the key role of disulfide bonds in driving the folding process highlighted in this research.
Article
Biochemistry & Molecular Biology
Lei Zhu, Hongxin Zhao, Juanjuan Liu, Hao Cai, Bo Wu, Zhijun Liu, Shu Zhou, Qingsong Liu, Xiaokun Li, Bin Bao, Jian Liu, Han Dai, Junfeng Wang
Summary: FGF21 is a regulator of glucose and lipid metabolism, and the designed FGF21(SS) chimera shows improved thermostability and effectiveness against T2DM through structural analysis and design.
Article
Biology
Lauren M. Ashwood, Khaled A. Elnahriry, Zachary K. Stewart, Thomas Shafee, Muhammad Umair Naseem, Tibor G. Szanto, Chloe A. van der Burg, Hayden L. Smith, Joachim M. Surm, Eivind A. B. Undheim, Bruno Madio, Brett R. Hamilton, Shaodong Guo, Dorothy C. C. Wai, Victoria L. Coyne, Matthew J. Phillips, Kevin J. Dudley, David A. Hurwood, Gyorgy Panyi, Glenn F. King, Ana Pavasovic, Raymond S. Norton, Peter J. Prentis
Summary: This study reveals the unique gene family SA8 in Actiniarians, which has therapeutic potential similar to the ShK toxin from Stichodactyla helianthus. The genomic arrangement and expression patterns of SA8 in Actinia tenebrosa and Telmatactis stephensoni were characterized, and the structure and function of SA8 in T. stephensoni venom were examined.
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
Biotechnology & Applied Microbiology
Mototaka Suzuki, Masayo Date, Tatsuki Kashiwagi, Eiichiro Suzuki, Keiichi Yokoyama
Summary: This study successfully improved the thermostability of microbial transglutaminase (MTG) through protein engineering and a structure-based approach. The most promising mutant, D3C/G283C, exhibited higher activity and longer half-life at high temperatures, which may expand its application in the food industry.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Austin B. Schwartz, Anshika Kapur, Zhenbo Huang, Raveendra Anangi, John M. Spear, Scott Stagg, Erminia Fardone, Zolan Dekan, Jens T. Rosenberg, Samuel C. Grant, Glenn F. King, Hedi Mattoussi, Debra Ann Fadool
Summary: The olfactory system is modulated by metabolic factors to drive changes in feeding behavior and energy homeostasis. Inhibiting Kv1.3 in the olfactory bulb can enhance excitability of output neurons and lead to metabolic responses, resulting in changes in body weight and energy metabolism.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
David A. Eagles, Chun Yuen Chow, Glenn F. King
Summary: This review examines the role of Na(V)1.7 channels in nociception, their history as a therapeutic target, and the challenges in developing potent inhibitors. Despite significant progress in drug development, effective analgesia remains elusive in clinical trials.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Matthew D. Figley, Weixi Gu, Jeffrey D. Nanson, Yun Shi, Yo Sasaki, Katie Cunnea, Alpeshkumar K. Malde, Xinying Jia, Zhenyao Luo, Forhad K. Saikot, Tamim Mosaiab, Veronika Masic, Stephanie Holt, Lauren Hartley-Tassell, Helen Y. McGuinness, Mohammad K. Manik, Todd Bosanac, Michael J. Landsberg, Philip S. Kerry, Mehdi Mobli, Robert O. Hughes, Jeffrey Milbrandt, Bostjan Kobe, Aaron DiAntonio, Thomas Ve
Summary: SARM1 is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme that is activated by an increase in the ratio of NMN to NAD+, triggering axon destruction. The structural analysis showed that both NMN and NAD+ compete for binding to the auto inhibitory N-terminal armadillo repeat (ARM) domain of SARM1.
Article
Food Science & Technology
Lauren M. Ashwood, Michela L. Mitchell, Bruno Madio, David A. Hurwood, Glenn F. King, Eivind A. B. Undheim, Raymond S. Norton, Peter J. Prentis
Summary: This study found that morphological variations in tentacles are associated with distinct toxin gene expression levels. Sea anemones with spherical tentacular structures may use specific venom cocktails to protect branched structures hosting a large number of photosynthetic symbionts.
Article
Biochemistry & Molecular Biology
Liping Liu, Richard M. Lucas, Jeffrey D. Nanson, Yan Li, Jason Whitfield, James E. B. Curson, Neeraj Tuladhar, Kirill Alexandrov, Mehdi Mobli, Matthew J. Sweet, Bostjan Kobe, Jennifer L. Stow, Lin Luo
Summary: In this study, we identify a novel immune-specific Syk scaffold protein SCIMP, which can contribute to inflammation through selective TLR-driven inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Volker Herzig, Yong-Cyuan Chen, Yanni K-Y Chin, Zoltan Dekan, Yu-Wang Chang, Hui-Ming Yu, Paul F. Alewood, Chien-Chang Chen, Glenn F. King
Summary: This study identified a tarantula venom from Avicularia spec. that can inhibit specific subtypes of T-type calcium channels, with the active toxin being omega-Avsp1a. The research suggests that omega-Avsp1a can inhibit specific subtypes of T-type calcium channels, and the domain-1 of Ca(V)3.3 is crucial for this inhibitory effect.
Article
Multidisciplinary Sciences
Biswaranjan Mohanty, Julien Orts, Geqing Wang, Stefan Nebl, Wesam S. Alwan, Bradley C. Doak, Martin L. Williams, Begona Heras, Mehdi Mobli, Martin J. Scanlon
Summary: The structures of protein-ligand complexes are crucial for drug design, and are mainly determined using X-ray crystallography. However, when crystallography fails, NMR is often used as an alternative method. Unfortunately, the tools available for rapid and robust structure determination of protein-ligand complexes by NMR are currently limited. In this study, the NMR2 approach is described, which allows the determination of the binding pose of a small molecule in a weak protein-ligand complex by collecting sparse protein methyl-to-ligand NOEs from a selectively labeled protein sample and an unlabeled ligand. This approach extends the utility of NMR2 to larger protein-ligand complexes.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Fernanda C. Cardoso, Sandy S. Pineda, Volker Herzig, Kartik Sunagar, Naeem Yusuf Shaikh, Ai-Hua Jin, Glenn F. King, Paul F. Alewood, Richard J. Lewis, Sebastien Dutertre
Summary: Australian tree-dwelling funnel-web spiders have venom that induces deadly symptoms and exhibits different venom composition compared to ground-dwelling species. The venom of tree-dwellers strongly modulates human voltage-gated sodium and calcium channels, while also showing potent insecticidal effects. This study contributes to understanding the molecular and pharmacological basis for severe envenomation by Australian tree-dwelling funnel-web spiders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michael D. Healy, Joanna Sacharz, Kerrie E. McNally, Calum McConville, Vikas A. Tillu, Ryan J. Hall, Molly Chilton, Peter J. Cullen, Mehdi Mobli, Rajesh Ghai, David A. Stroud, Brett M. Collins
Summary: SNX17 controls the endosomal recycling of transmembrane cargo proteins through its association with the Commander trafficking complex and the PDLIM family of proteins. The interaction between SNX17 and PDLIM is mediated by a unique peptide interaction involving electrostatic contacts and a conserved proline-containing loop sequence. This interaction may play a role in regulating the activity of SNX17 in conjunction with Commander and actin-rich endosomal trafficking domains.
Article
Biochemistry & Molecular Biology
Junyu Liu, Michael Maxwell, Thom Cuddihy, Theo Crawford, Madeline Bassetti, Cameron Hyde, Steve Peigneur, Jan Tytgat, Eivind A. B. Undheim, Mehdi Mobli
Summary: Receptor avidity through multivalency is difficult to engineer in synthetic molecules, but can be found in natural bivalent antibodies. The discovery of bivalent venom peptides with tandem repeat domains has provided insight into multivalency in biomolecules. ScrepYard, an online resource, assists in identifying SCREP sequences and characterizing this emerging class of biomolecules.
Article
Biochemical Research Methods
Qiushi Cao, Cheng Ge, Xuejie Wang, Peta J. Harvey, Zixuan Zhang, Yuan Ma, Xianghong Wang, Xinying Jia, Mehdi Mobli, David J. Craik, Tao Jiang, Jinbo Yang, Zhiqiang Wei, Yan Wang, Shan Chang, Rilei Yu
Summary: With the rise of multidrug-resistant bacteria, antimicrobial peptides (AMPs) have emerged as potential alternatives to traditional antibiotics for treating bacterial infections. However, traditional methods of discovering and designing AMPs are time-consuming and costly. This study utilized deep learning techniques, including sequence generative adversarial nets, bidirectional encoder representations from transformers, and multilayer perceptron, to design and identify AMPs. Six candidate AMPs were then screened and one of them, A-222, showed inhibition against both gram-positive and gram-negative bacteria. Structural analysis and subsequent structure-activity relationship studies led to the design of peptide analogs with increased activity against specific bacteria. Overall, deep learning holds great promise in accelerating the discovery of novel AMPs and could have significant implications in developing new antimicrobial treatments.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Andrew A. Walker, Lynda E. Perkins, Andrea Battisti, Myron P. Zalucki, Glenn F. King
Summary: Ochrogaster lunifer is an Australian caterpillar that has detachable urticating setae with defensive function. These setae can cause inflammation on human skin and equine foetal loss syndrome in gravid horses if accidentally ingested. Transcriptomics and proteomics analysis identified 37 putative toxins, including multiple homologues of honeybee venom peptide secapin and proteins with similarity to odorant binding proteins, arylphorins, and the insect immune modulator Diedel. This study reveals candidate molecules that may contribute to the adverse effects of processionary caterpillar setae on human and animal health.
Article
Chemistry, Multidisciplinary
Xinying Jia, Yanni K. -Y. Chin, Alan H. H. Zhang, Theo Crawford, Yifei Zhu, Nicholas L. L. Fletcher, Zihan Zhou, Brett R. R. Hamilton, Martin Stroet, Kristofer J. J. Thurecht, Mehdi Mobli
Summary: The authors report the engineering of self-cyclizing 'autocyclase' proteins to generate macrocyclic peptides and proteins with favorable reaction kinetics for suppressing polymerization. Macrocyclisation of proteins and peptides results in a remarkable increase in structural stability, making cyclic peptides and proteins of great interest in drug discovery. The engineering of a self-cyclising autocyclase protein provides a simple, alternative way to access a vast diversity of macrocyclic biomolecules.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gagan Sharma, Carolyne B. Braga, Kai-En Chen, Xinying Jia, Venkatraman Ramanujam, Brett M. Collins, Roberto Rittner, Mehdi Mobli
Summary: Chlorotoxin (ClTx) is a disulfide-rich peptide isolated from scorpion venom that selectively binds to brain tumors and has emerged as a potential target for the vascular endothelial growth factor receptor, neuropilin-1 (NRP1). This study characterized the binding details of ClTx to NRP1 through NMR spectroscopy, revealing a non-standard binding motif that provides a basis for future engineering of ClTx for improved applications.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
