Riccardo Dejoma, Andrea Buscemi, Emilio Cutrona, Patrick Shahgaldian
{"title":"Design of a Biocatalytic Flow Reactor Based on Hierarchically Structured Monolithic Silica for Producing Galactooligosaccharides (GOSs).","authors":"Riccardo Dejoma, Andrea Buscemi, Emilio Cutrona, Patrick Shahgaldian","doi":"10.2533/chimia.2023.432","DOIUrl":"10.2533/chimia.2023.432","url":null,"abstract":"<p><p>Climate change mitigation requires the development of greener chemical processes. In this context, biocatalysis is a pivotal key enabling technology. The advantages of biocatalysis include lower energy consumption levels, reduced hazardous waste production and safer processes. The possibility to carry out biocatalytic reactions under flow conditions provides the additional advantage to retain the biocatalyst and to reduce costly downstream processes. Herein, we report a method to produce galactooligosaccharides (GOSs) from a largely available feedstock (i.e. lactose from dairy production) using a flow reactor based on hierarchically structured monolithic silica. This reactor allows for fast and efficient biotransformation reaction in flow conditions.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"274 1","pages":"432-436"},"PeriodicalIF":1.2,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89208635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interactions of Na<sup>+</sup>/taurocholate cotransporting polypeptide with host cellular proteins upon hepatitis B and D virus infection: novel potential targets for antiviral therapy.","authors":"Dariusz Zakrzewicz, Joachim Geyer","doi":"10.1515/hsz-2022-0345","DOIUrl":"https://doi.org/10.1515/hsz-2022-0345","url":null,"abstract":"<p><p>Na<sup>+</sup>/taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier (SLC) family 10 transporters (gene symbol <i>SLC10A1</i>) and is responsible for the sodium-dependent uptake of bile salts across the basolateral membrane of hepatocytes. In addition to its primary transporter function, NTCP is the high-affinity hepatic receptor for hepatitis B (HBV) and hepatitis D (HDV) viruses and, therefore, is a prerequisite for HBV/HDV virus entry into hepatocytes. The inhibition of HBV/HDV binding to NTCP and internalization of the virus/NTCP receptor complex has become a major concept in the development of new antiviral drugs called HBV/HDV entry inhibitors. Hence, NTCP has emerged as a promising target for therapeutic interventions against HBV/HDV infections in the last decade. In this review, recent findings on protein-protein interactions (PPIs) between NTCP and cofactors relevant for entry of the virus/NTCP receptor complex are summarized. In addition, strategies aiming to block PPIs with NTCP to dampen virus tropism and HBV/HDV infection rates are discussed. Finally, this article suggests novel directions for future investigations evaluating the functional contribution of NTCP-mediated PPIs in the development and progression of HBV/HDV infection and subsequent chronic liver disorders.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"673-690"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10146509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid exchange among electroneutral Sulfo-DIBMA nanodiscs is independent of ion concentration.","authors":"Loretta Eggenreich, Carolyn Vargas, Cenek Kolar, Sandro Keller","doi":"10.1515/hsz-2022-0319","DOIUrl":"https://doi.org/10.1515/hsz-2022-0319","url":null,"abstract":"<p><p>Polymer-encapsulated nanodiscs enable membrane proteins to be investigated within a native-like lipid-bilayer environment. Unlike other bilayer-based membrane mimetics, these nanodiscs are equilibrium structures that permit lipid exchange on experimentally relevant timescales. Therefore, examining the kinetics and mechanisms of lipid exchange is of great interest. Since the high charge densities of existing anionic polymers can interfere with protein-protein and protein-lipid interactions as well as charge-sensitive analysis techniques, electroneutral nanodisc-forming polymers have been recently introduced. However, it has remained unclear how the electroneutrality of these polymers affects the lipid-exchange behavior of the nanodiscs. Here, we use time-resolved Förster resonance energy transfer to study the kinetics and the mechanisms of lipid exchange among nanodiscs formed by the electroneutral polymer Sulfo-DIBMA. We also examine the role of coulombic repulsion and specific counterion association in lipid exchange. Our results show that Sulfo-DIBMA nanodiscs exchange lipids on a similar timescale as DIBMA nanodiscs. In contrast with nanodiscs made from polyanionic DIBMA, however, the presence of mono- and divalent cations does not influence lipid exchange among Sulfo-DIBMA nanodiscs, as expected from their electroneutrality. The robustness of Sulfo-DIBMA nanodiscs against varying ion concentrations opens new possibilities for investigating charge-sensitive processes involving membrane proteins.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"703-713"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10263143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biological ChemistryPub Date : 2023-06-27Print Date: 2024-01-29DOI: 10.1515/hsz-2023-0172
Sarah Janice Hörner, Nathalie Couturier, Mathias Hafner, Rüdiger Rudolf
{"title":"Schwann cells in neuromuscular <i>in vitro</i> models.","authors":"Sarah Janice Hörner, Nathalie Couturier, Mathias Hafner, Rüdiger Rudolf","doi":"10.1515/hsz-2023-0172","DOIUrl":"10.1515/hsz-2023-0172","url":null,"abstract":"<p><p>Neuromuscular cell culture models are used to investigate synapse formation and function, as well as mechanisms of de-and regeneration in neuromuscular diseases. Recent developments including 3D culture technique and hiPSC technology have propelled their ability to complement insights from <i>in vivo</i> models. However, most cultures have not considered Schwann cells, the glial part of NMJs. In the following, a brief overview of different types of neuromuscular cocultures is provided alongside examples for studies that included Schwann cells. From these, findings concerning the effects of Schwann cells on those cultures are summarized and future lines of research are proposed.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"25-30"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anja Roden, Melanie K Engelin, Klaas M Pos, Eric R Geertsma
{"title":"Membrane-anchored substrate binding proteins are deployed in secondary TAXI transporters.","authors":"Anja Roden, Melanie K Engelin, Klaas M Pos, Eric R Geertsma","doi":"10.1515/hsz-2022-0337","DOIUrl":"https://doi.org/10.1515/hsz-2022-0337","url":null,"abstract":"<p><p>Substrate-binding proteins (SBPs) are part of solute transport systems and serve to increase substrate affinity and uptake rates. In contrast to primary transport systems, the mechanism of SBP-dependent secondary transport is not well understood. Functional studies have thus far focused on Na<sup>+</sup>-coupled Tripartite ATP-independent periplasmic (TRAP) transporters for sialic acid. Herein, we report the <i>in vitro</i> functional characterization of TAXIPm-PQM from the human pathogen <i>Proteus mirabilis</i>. TAXIPm-PQM belongs to a TRAP-subfamily using a different type of SBP, designated TRAP-associated extracytoplasmic immunogenic (TAXI) protein. TAXIPm-PQM catalyzes proton-dependent α-ketoglutarate symport and its SBP is an essential component of the transport mechanism. Importantly, TAXIPm-PQM represents the first functionally characterized SBP-dependent secondary transporter that does not rely on a soluble SBP, but uses a membrane-anchored SBP instead.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"715-725"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mycobacterial type VII secretion systems.","authors":"Nikolaos Famelis, Sebastian Geibel, Daan van Tol","doi":"10.1515/hsz-2022-0350","DOIUrl":"https://doi.org/10.1515/hsz-2022-0350","url":null,"abstract":"<p><p>Mycobacteria, such as the pathogen <i>M. tuberculosis</i>, utilize up to five paralogous type VII secretion systems to transport proteins across their cell envelope. Since these proteins associate in pairs that depend on each other for transport to a different extent, the secretion pathway to the bacterial surface remained challenging to address. Structural characterization of the inner-membrane embedded secretion machineries along with recent advances on the substrates' co-dependencies for transport allow for the first time more detailed and testable models for secretion.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"691-702"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Mann, Kristin Labudda, Sophie Zimmermann, Kai Ulrich Vocke, Raphael Gasper, Carsten Kötting, Eckhard Hofmann
{"title":"ATP binding and ATP hydrolysis in full-length MsbA monitored via time-resolved Fourier transform infrared spectroscopy.","authors":"Daniel Mann, Kristin Labudda, Sophie Zimmermann, Kai Ulrich Vocke, Raphael Gasper, Carsten Kötting, Eckhard Hofmann","doi":"10.1515/hsz-2023-0122","DOIUrl":"https://doi.org/10.1515/hsz-2023-0122","url":null,"abstract":"<p><p>The essential <i>Escherichia coli</i> ATPase MsbA is a lipid flippase that serves as a prototype for multi drug resistant ABC transporters. Its physiological function is the transport of lipopolisaccharides to build up the outer membranes of Gram-negative bacteria. Although several structural and biochemical studies of MsbA have been conducted previously, a detailed picture of the dynamic processes that link ATP hydrolysis to allocrit transport remains elusive. We report here for the first time time-resolved Fourier transform infrared (FTIR) spectroscopic measurements of the ATP binding and ATP hydrolysis reaction of full-length MsbA and determined reaction rates at 288 K of <i>k</i> <sub>1</sub> = 0.49 ± 0.28 s<sup>-1</sup> and <i>k</i> <sub>2</sub> = 0.014 ± 0.003 s<sup>-1</sup>, respectively. We further verified these rates with photocaged NPE<i>cg</i>AppNHp where only nucleotide binding was observable and the negative mutant MsbA-H537A that showed slow hydrolysis (<i>k</i> <sub>2</sub> < 2 × 10<sup>-4</sup> s<sup>-1</sup>). Besides single turnover kinetics, FTIR measurements also deliver IR signatures of all educts, products and the protein. ADP remains protein-bound after ATP hydrolysis. In addition, the spectral changes observed for the two variants MsbA-S378A and MsbA-S482A correlated with the loss of hydrogen bonding to the γ-phosphate of ATP. This study paves the way for FTIR-spectroscopic investigations of allocrite transport in full-length MsbA.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"727-737"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interaction of RTX toxins with the host cell plasma membrane.","authors":"Feby M Chacko, Lutz Schmitt","doi":"10.1515/hsz-2022-0336","DOIUrl":"https://doi.org/10.1515/hsz-2022-0336","url":null,"abstract":"<p><p><b>R</b>epeats in <b>T</b>o<b>X</b>ins (RTX) protein family is a group of exoproteins secreted by Type 1 secretion system (T1SS) of several Gram-negative bacteria. The term RTX is derived from the characteristic nonapeptide sequence (GGxGxDxUx) present at the C-terminus of the protein. This RTX domain binds to calcium ions in the extracellular medium after being secreted out of the bacterial cells, and this facilitates folding of the entire protein. The secreted protein then binds to the host cell membrane and forms pores via a complex pathway, which eventually leads to the cell lysis. In this review, we summarize two different pathways in which RTX toxins interact with host cell membrane and discuss the possible reasons for specific and unspecific activity of RTX toxins to different types of host cells.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 7","pages":"663-671"},"PeriodicalIF":3.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biological ChemistryPub Date : 2023-06-26Print Date: 2023-09-26DOI: 10.1515/hsz-2023-0169
Robert Dörrenhaus, Philip K Wagner, Stephanie Kath-Schorr
{"title":"Two are not enough: synthetic strategies and applications of unnatural base pairs.","authors":"Robert Dörrenhaus, Philip K Wagner, Stephanie Kath-Schorr","doi":"10.1515/hsz-2023-0169","DOIUrl":"10.1515/hsz-2023-0169","url":null,"abstract":"<p><p>Nucleic acid chemistry is a rapidly evolving field, and the need for novel nucleotide modifications and artificial nucleotide building blocks for diagnostic and therapeutic use, material science or for studying cellular processes continues unabated. This review focusses on the development and application of unnatural base pairs as part of an expanded genetic alphabet. Not only recent developments in \"nature-like\" artificial base pairs are presented, but also current synthetic methods to get access to C-glycosidic nucleotides. Wide-ranging viability in synthesis is a prerequisite for the successful use of unnatural base pairs in a broader spectrum and will be discussed.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"404 10","pages":"883-896"},"PeriodicalIF":3.7,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10272302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}