Sean Dowd, Luke Lagalante, Jack Rahlfs, Catherine Sharo, Dana Opulente, Anthony Lagalante, Jacob Elmer
The erythrocruorin of Lumbricus terrestris (LtEc) is a relatively large macromolecular assembly that consists of at least four different hemoglobin subunits (A, B, C, and D) and four linker subunits (L1, L2, L3, and L4). The complexity and stability of this large structure make LtEc an attractive hemoglobin-based oxygen carrier that could potentially be used as a substitute for donated red blood cells. However, the sequences of the LtEc subunit sequences must be determined before a scalable recombinant expression platform can be developed...
November 17, 2023: Biochimie
Kazuya Tanabe, Kouichi Miyazaki, Hikari Umeno, Marina Takemoto, Shu-Ichi Nakano
The human genome contains many G-quadruplex-forming sequences, including sequences containing long single-stranded loops that are believed to be unfavorable for G-quadruplex formation. The intracellular environment of biological cells is crowded with proteins with charged surfaces. Understanding the effects of protein-rich environments is important for understanding the formation of G-quadruplexes in an intracellular environment. In this study, we investigated the structural stability of DNA G-quadruplexes in the presence of several types of globular proteins (lysozyme, cytochrome c, bovine serum albumin, myoglobin, histone proteins, and serum proteins), unstructured polypeptides (protamine and poly-l-lysine), and oligopeptides (RGG/RG-domain peptides and short repeated peptides)...
November 14, 2023: Biochimie
Shirsha Mondal, Arindam Bandyopadhyay
Glucose transporters (GLUTs) are crucial in maintaining glucose homeostasis and supporting energy production in various tissues, including the testes. This review article delves into the distribution and function of GLUTs in distinct testicular cell types, namely Leydig cells, Sertoli cells, germ cells, and spermatozoa, shedding light on their significance in the context of male reproductive health-an issue of mounting global concern. Furthermore, this manuscript examines the implications of GLUT dysregulation in testicular dysfunction...
November 13, 2023: Biochimie
Richard Buckingham, Yoshikazu Nakamura
No abstract text is available yet for this article.
November 13, 2023: Biochimie
Burak V Kabasakal, Charles A R Cotton, James W Murray
Malonyl-Coenzyme A Reductase (MCR) in Chloroflexus aurantiacus, a characteristic enzyme of the 3-hydroxypropionate (3-HP) cycle, catalyses the reduction of malonyl-CoA to 3-HP. MCR is a bi-functional enzyme; in the first step, malonyl-CoA is reduced to the free intermediate malonate semialdehyde by the C-terminal region of MCR, and this is further reduced to 3-HP by the N-terminal region of MCR. Here we present the crystal structures of both N-terminal and C-terminal regions of the MCR from C. aurantiacus. A catalytic mechanism is suggested by ligand and substrate bound structures, and structural and kinetic studies of MCR variants...
November 10, 2023: Biochimie
Ish Kumar, Melissa Silva, Dinesh A Choudhary, Syeda F Ali, Raymond Rusak, Paulina Cotzomi, Suzanne Wiecek, Iwon Sato, Rinat Khundoker, Bora Donmez, Samantha Gabriel, Monica Bobila, Mihaela D Leonida, Christian Traba
Matrix metalloproteinases (MMPs) are endopeptidases, and their activity depends on calcium and zinc metal ions. These enzymes are expressed originally in zymogenic form, where the active site of proteins is closed by a prodomain which is removed during activation. A homeostatic balance of their activity is primarily regulated by a 'cysteine switch' located on a consensus sequence of the prodomain and natural endogenous inhibitors, called tissue inhibitors of metalloproteinases (TIMPs). Breakage of this homeostasis may lead to various pathological conditions, which may require further activation and/or inhibition of these enzymes to regenerate that balance...
November 7, 2023: Biochimie
Rawayh Albaghlany, Mohammad Bagher Shahsavani, Masaru Hoshino, Ali Akbar Moosavi-Movahedi, Younes Ghasemi, Reza Yousefi
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that reduces postprandial glycemic excursions by enhancing insulin secretion. In this study, a new dimeric GLP-1 analogue (GLP-1cpGLP-1) was designed by inserting human insulin C-peptide (CP) in the middle of a dimer of [Gly8] GLP-1 (7-36). Then, the dimeric incretin (GLP-1cpGLP-1) was ligated to human αB-crystallin (αB-Cry) to create a hybrid protein, abbreviated as αB-GLP-1cpGLP-1. The constructed gene was well expressed in the bacterial host system...
November 4, 2023: Biochimie
Maryam Adelipour, Hyojin Hwang, Dokyung Kwon, Kee K Kim, Jeong Hee Moon, David M Lubman, Jeongkwon Kim
Mesenchymal stem cells (MSCs) have potential as a viable treatment option in the field of regenerative medicine, but MSC-based therapy needs to be more efficient. Preconditioning is a method to improve MSC-based therapy, and dimethyl fumarate (DMF) - an agent that can enhance the antioxidative capacity of cells - can be considered for preconditioning of MSCs. In this study, we treated bone marrow-derived MSCs with DMF and evaluated their proteome using bottom-up proteomics. The MSCs were exposed to 10 μM DMF for 24 h, followed by lysis with an SDS solution, digestion with trypsin using an s-trap column, and analysis using nanoLC-MS/MS, which identified 2262 proteins with confidence...
November 4, 2023: Biochimie
TatyanaS Iurchenko, Seseg B Bolotova, Anastasia A Loginova, Ivan S Kargov, Denis L Atroshenko, Svyatoslav S Savin, Evgenii V Pometun, Vladimir I Tishkov, Anastasia A Pometun
NAD+ -dependent formate dehydrogenase (FDH, EC from the bacterium Staphylococcus aureus (SauFDH) plays an important role in the vital activity of this bacterium, especially in the form of biofilms. Understanding its mechanism and structure-function relationship can help to find special inhibitors of this enzyme, which can be used as medicines against staphylococci. The gene encoding SauFDH was successfully cloned and expressed in our laboratory. This enzyme has the highest kcat value among the described FDHs and also has a high temperature stability compared to other enzymes of this group...
November 2, 2023: Biochimie
Kun Ji, Yufan Yao, Yuxuan Gao, Sujie Huang, Ling Ma, Qing Pan, Jun Wu, Wei Zhang, Hongmei Chen, Lei Zhang
TP10, a classic cell-penetrating peptide, shows a high degree of similarity to AMPs in structure. Although TP10 has been widely used in drug delivery, the mechanism underlying its cytotoxicity is yet to be elucidated. Herein, we explored the cell-killing mechanism of TP10 against human leukemia Jurkat cells. TP10 induced necrosis in Jurkat cells via rapid disruption of cell membranes, particularly at high concentrations. Although mitochondria in Jurkat cells were damaged by TP10, mitochondria-mediated apoptosis did not occur, possibly due to intracellular ATP depletion...
November 1, 2023: Biochimie
Manisekaran Hemagirri, Yeng Chen, Subash C B Gopinath, Sumaira Sahreen, Mohd Adnan, Sreenivasan Sasidharan
Maintaining the proteome is crucial to retaining cell functionality and response to multiple intrinsic and extrinsic stressors. Protein misfolding increased the endoplasmic reticulum (ER) stress and activated the adaptive unfolded protein response (UPR) to restore cell homeostasis. Apoptosis occurs when ER stress is prolonged or the adaptive response fails. In healthy young cells, the ratio of protein folding machinery to quantities of misfolded proteins is balanced under normal circumstances. However, the age-related deterioration of the complex systems for handling protein misfolding is accompanied by ageing-related disruption of protein homeostasis, which results in the build-up of misfolded and aggregated proteins...
October 31, 2023: Biochimie
Vanessa Zarzosa, Bruno Lomonte, Fernando Zamudio, Roberto Ponce-López, Felipe Olvera-Rodríguez, Miguel Borja, Alejandro Alagón, Edgar Neri-Castro
Crotalus culminatus is a medically significant species of rattlesnake in Mexico [1]. While the proteomic composition of its venom has been previously reported for both juvenile and adult specimens, there has been limited research into its functional properties, with only a few studies, including one focusing on coagulotoxicity mechanisms. In this study, we aimed to compare the biochemical and biological activities of the venom of juvenile and adult snakes. Additionally, we assessed antibody production using the venoms of juveniles and adults as immunogens in rabbits...
October 25, 2023: Biochimie
Ana Laura Granados-Tristán, Carlos Eduardo Hernández-Luna, Laura Adiene González-Escalante, María Elena Camacho-Moll, Beatriz Silva-Ramírez, Mario Bermúdez de León, Katia Peñuelas-Urquides
Mycobacteria are microorganisms distributed in the environment worldwide, and some of them, such as Mycobacterium tuberculosis or M. leprae, are pathogenic. The hydrophobic mycobacterial cell envelope has low permeation and bacteria need to export products across their structure. Mycobacteria possess specialized protein secretion systems, such as the Early Secretory Antigenic Target 6 secretion (ESX) system. Five ESX loci have been described in M. tuberculosis, called ESX1 to ESX5. The ESX3 secretion system has been associated with mycobacterial metabolism and growth...
October 23, 2023: Biochimie
Verónica Bastos, Simone Pascoal, Kamila Lopes, Márcia Mortari, Helena Oliveira
Cancer is a huge public health problem being one of the main causes of death globally. Specifically, melanoma is one of the most threatening cancer types due to the metastatic capacity, treatment resistance and mortality rates. It is evident the urgent need for research on new agents with pharmacological potential for cancer treatment, in order to develop new cancer therapeutic strategies and overcome drug resistance. The present work investigated the anti-tumoral potential of Chartergellus-CP1 peptide, isolated from Chartergellus communis wasp venom on human melanoma cell lines with different pigmentation degrees, namely the amelanotic cell line A375 and pigmented cell line MNT-1...
October 23, 2023: Biochimie
Elvira R Shaykhutdinova, Maria S Severyukhina, Inna V Kholoshenko, Elena A Gondarenko, Irina V Shelukhina, Elena V Kryukova, Alina M Ismailova, Elena S Sadovnikova, Igor A Dyachenko, Arkady N Murashev, Victor I Tsetlin, Yuri N Utkin
Evidence to date indicates that activation of nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury from ischemia and subsequent reperfusion. The use of nAChR agonists in various animal models leads to a reduction in reperfusion injury. Earlier this effect was shown for the agonists of α7 nAChR subtype. In this work, we demonstrated the expression of mRNA encoding α4, α6 and β2 nAChR subunits in the left ventricle of rat heart. In a rat model of myocardial ischemia, we studied the effect of α4β2 nAChR agonists cytisine and varenicline, medicines used for the treatment of nicotine addiction, and found them to significantly reduce myocardium ischemia-reperfusion injury, varenicline manifesting a higher protection...
October 21, 2023: Biochimie
Anna E Pravednikova, Antonina Nikitich, Agata Witkowicz, Lidia Karabon, Andreas D Flouris, Maria Vliora, Eleni Nintou, Petros C Dinas, Monika Szulińska, Paweł Bogdański, George S Metsios, Victor V Kerchev, Levon Yepiskoposyan, Oleg V Bylino, Svetlana N Larina, Boris Shulgin, Yulii V Shidlovskii
Cardiometabolic diseases (CMDs) are complex disorders with a heterogenous phenotype, which are caused by multiple factors including genetic factors. Single nucleotide polymorphisms (SNPs) rs45539933 (p.Ala64Thr), rs10011540 (c.-112A>C), rs3811791 (c.-1766A>G), and rs1800592 (c.-3826A>G) in the UCP1 gene have been analyzed for association with CMDs in many studies providing controversial results. However, previous studies only considered individual UCP1 SNPs and did not evaluate them in an integrated manner, which is a more powerful approach to uncover genetic component of complex diseases...
October 18, 2023: Biochimie
Ya-Nan Ou-Yang, Fen-Fen Deng, Yun-Jia Wang, Meng Chen, Peng-Fei Yang, Zhe Yang, Zhongmin Tian
A high-salt diet is known to increase serum cholesterol levels; however, the underlying mechanism of salt-induced dyslipidemia in patients with salt-sensitivity remains poorly understood. We aimed to investigate whether high-salt diet (HSD) can induce dyslipidemia and elucidate the underlying mechanism of salt-induced dyslipidemia in Dahl salt-sensitive (SS) rats. Metabolomic and biochemical analyses revealed that the consumption of an HSD (8 % NaCl) significantly increased the serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in SS rats...
October 14, 2023: Biochimie
Juan Diego Piedrahita, Ana Cardona-Ruda, Jaime Andrés Pereañez, Paola Rey-Suárez
In Colombia, the Micrurus genus comprises 30 species, including M. mipartitus and M. dumerilii, which are of major clinical relevance due to their wide geographical distribution and the number of snakebites inflicted by them. These neurotoxic envenomations are characterized by neuromuscular paralysis attributed to venom components such as three-finger toxins (3FTx) and phospholipases (PLA2 ). Additionally, there is limited information available on the neutralizing coverage of commercially available antivenoms, underscoring the need to perform studies to assess the cross-neutralizing ability of these life-saving products...
October 14, 2023: Biochimie
Jackson Gabriel Miyamoto, Eduardo Shigueo Kitano, André Zelanis, Pedro Gabriel Nachtigall, Inácio Junqueira-de-Azevedo, Sávio Stefanini Sant'Anna, Rogério Lauria da Silva, Patrícia Alessandra Bersanetti, Adriana Karaoglanovic Carmona, Pedro José Barbosa Pereira, Solange Maria de Toledo Serrano, Maria Luiza Vilela Oliva, Alexandre Keiji Tashima
Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin...
October 14, 2023: Biochimie
Matúš Vojsovič, Libuše Kratochvilová, Natália Valková, Lucie Šislerová, Zeinab El Rashed, Paola Menichini, Alberto Inga, Paola Monti, Václav Brázda
The effect of mutations in the P53 family of transcription factors on their biological functions, including partial or complete loss of transcriptional activity, has been confirmed several times. At present, P53 family proteins showing partial loss of activity appear to be promising potential candidates for the development of novel therapeutic strategies which could restore their transcriptional activity. In this context, it is important to employ tools to precisely monitor their activity; in relation to this, non-canonical DNA secondary structures in promoters including G-quadruplexes (G4s) were shown to influence the activity of transcription factors...
October 12, 2023: Biochimie
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