ChemBioChemPub Date : 2025-02-18DOI: 10.1002/cbic.202500018
Tomonori Kimura, Shinsuke Sakai, Yoshitaka Isaka
{"title":"d-Alanine, a Circadian Metabolite that Regulates Glucose Metabolism and Viral Infection.","authors":"Tomonori Kimura, Shinsuke Sakai, Yoshitaka Isaka","doi":"10.1002/cbic.202500018","DOIUrl":"10.1002/cbic.202500018","url":null,"abstract":"<p><p>d-Alanine, a rare d-amino acid, exhibits a clear circadian rhythm and is present in organs associated with glucose metabolism. Recent findings have revealed that d-alanine acts on the circadian rhythm, thereby regulating physiological processes related to circadian cycles that are essential for maintaining body homeostasis. The regulation of circadian rhythm by d-alanine is vital for correcting blood glucose levels in diabetic conditions. In viral infections, d-alanine serves as a sensitive biomarker that reflects the severity of the infection, as its level drastically decreases due to consumption. Supplementation with d-alanine is effective to alleviate the progression of viral infections, potentially through the maintenance of the circadian rhythm and its associated immune responses. In addition to its role as a circadian biomarker, d-alanine also functions as a circadian regulator and exerts a wide range of physiological effects. This review summarizes the physiological roles of d-alanine as a circadian metabolite.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500018"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447795","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}
ChemBioChemPub Date : 2025-02-17DOI: 10.1002/cbic.202400832
Siti Fatimah Nur Abdul Aziz, Abu Bakar Salleh, Yahaya M Normi, Shahrul Ainliah Alang Ahmad
{"title":"Linker Ratio-Dependent Physicochemical Properties of ZIF-8 Encapsulated Mini Protein 20 Mimicking Uricase.","authors":"Siti Fatimah Nur Abdul Aziz, Abu Bakar Salleh, Yahaya M Normi, Shahrul Ainliah Alang Ahmad","doi":"10.1002/cbic.202400832","DOIUrl":"10.1002/cbic.202400832","url":null,"abstract":"<p><p>Despite a growing interest in zeolitic imidazolate framework-8 (ZIF-8), notably for their potential as a host for various bio- and molecules, including peptides, the critical factors affecting their physicochemical properties and encapsulation efficiency are relatively unknown, limiting their widespread use. Herein, mini protein 20 (mp20), biomolecule mimicking uricase was used as a model to be hosted within ZIF-8 (mp20@ZIF-8) biocomposites. ZIF-8 were synthesized over a range of molar ratio of Zn to 2-methylimidazole(2-HmIm). By systematically exploring the impacts of various linker ratios, we found that a Zn to 2-HmIm ratio of 1 : 4 offers the highest encapsulation efficiency and thermal stability, making it particularly suitable for applications where these properties are critical. The 1 : 8 ratio, on the other hand, makes biocomposites with the most crystallized and a well-balanced combination of particle size and surface area, which are advantageous for applications requiring high structural integrity and surface interaction. This approach not only advances our understanding of protein encapsulation in MOFs but also provides new insights into how the linker-to-metal ratio can be optimized for different applications. Subsequent studies could expand upon these findings by implementing the enhanced biocomposites in practical applications, examining the encapsulation of biomolecules, or assessing the durability the long-term stability and functionality of these materials in various conditions.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400832"},"PeriodicalIF":2.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439334","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}
ChemBioChemPub Date : 2025-02-17DOI: 10.1002/cbic.202400959
Konstantin Neißner, Carolin Frohnapfel, Heiko Keller, Elke Duchardt-Ferner, Vanessa Schneider, Zeinab Kamjou, Beate Averhoff, Jens Wöhnert
{"title":"NMR Solution Structure of the N-Terminal GSPII Domain from the Thermus Thermophilus Traffic ATPase PilF and Reconstruction of its c-di-GMP Binding Capability.","authors":"Konstantin Neißner, Carolin Frohnapfel, Heiko Keller, Elke Duchardt-Ferner, Vanessa Schneider, Zeinab Kamjou, Beate Averhoff, Jens Wöhnert","doi":"10.1002/cbic.202400959","DOIUrl":"10.1002/cbic.202400959","url":null,"abstract":"<p><p>The cyclic dinucleotide c-di-GMP is an important second messenger molecule in bacteria and interacts with a variety of receptor molecules including RNA and protein domains. An important class of c-di-GMP-binding protein domains are the general secretory pathway type II (GSPII) domains as exemplified by the N-terminal domain of the ATPase MshE from Vibrio cholerae (MshEN). MshEN binds monomeric c-di-GMP via two consecutive copies of a 24-residue sequence motif, which form a compact 4-α-helical bundle. The ATPase PilF from Thermus thermophilus regulates pilus formation, motility and DNA-uptake. Its N-terminal section contains three consecutive GSPII domains (GSPII-A-GSPII-C) all with considerable sequence homology to MshEN. While the GSPII-B and the GSPII-C domains bind c-di-GMP, the GSPII-A domain does not. To determine why it is incapable of c-di-GMP-binding we determined the NMR-solution structure of this domain. Our structure shows how small deviations in the consensus motif sequence, a stabilizing N-terminal helical capping motif and intersubdomain interactions absent in MshEN cooperate to prevent c-di-GMP-binding. By combining point mutations and truncations, we re-established the c-di-GMP binding capability. Our findings shed new light on the evolution and functional diversification of GSPII domains and the importance of sequence variations for protein activity in this domain family.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400959"},"PeriodicalIF":2.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439339","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}
ChemBioChemPub Date : 2025-02-14DOI: 10.1002/cbic.202500022
Mariam El-Morched, Jesse Vanloon, Frank Wien, Thad Harroun, Hongbin Yan
{"title":"Structural Study of DNA in Simulated Crowded Fluids.","authors":"Mariam El-Morched, Jesse Vanloon, Frank Wien, Thad Harroun, Hongbin Yan","doi":"10.1002/cbic.202500022","DOIUrl":"10.1002/cbic.202500022","url":null,"abstract":"<p><p>This work studied the structure and hybridization properties of DNA in simulated crowded media containing polyethylene glycol 10,000 and sucrose. Synchrotron radiation circular dichroism revealed that the overall CD profiles of a 21-mer and a d(CG)<sub>9</sub> duplex remain similar in the simulated crowded fluids compared with those in Tris buffer, but the amplitude ratios of individual maxima and minima vary with the concentration of DNA and the media, suggesting possible conformational changes. Using fluorescence resonance energy transfer, this work confirmed that hairpin and duplex formations are not affected by the crowding condition. On the other hand, the duplex dynamics is affected by the crowding condition, where strand exchanges were promoted by the presence of PEG, but unaffected by sucrose.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500022"},"PeriodicalIF":2.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416918","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202580301
Ms. Melody Cai-Syaun Wu, Mr. Jack Hau-Ting Wei, Mr. Ricky Yu-Syun Fan, Ms. Eng Zhi Sim, Prof. Ken-Tye Yong, Prof. Tianxun Gong, Prof. Kien Voon Kong
{"title":"Front Cover: Self-Assembled BODIPY@Au Core-Shell Structures for Durable Neuroprotective Phototherapy (ChemBioChem 3/2025)","authors":"Ms. Melody Cai-Syaun Wu, Mr. Jack Hau-Ting Wei, Mr. Ricky Yu-Syun Fan, Ms. Eng Zhi Sim, Prof. Ken-Tye Yong, Prof. Tianxun Gong, Prof. Kien Voon Kong","doi":"10.1002/cbic.202580301","DOIUrl":"https://doi.org/10.1002/cbic.202580301","url":null,"abstract":"<p>Exciting breakthrough in neuroprotective phototherapy! Introducing Bpy-BODIPY@Au, a cutting-edge nanophotosensitizer designed to enhance treatment for neurodegenerative diseases. By using the J-aggregation of BODIPY on gold nanourchins, this innovative structure boosts singlet oxygen production and photostability, effectively reducing tau protein aggregation—a key factor in Alzheimer′s disease. This promising therapeutic approach expands the use of BODIPY-based nanoagents in treating neurodegenerative conditions, showcasing their potential for durable and targeted phototherapy. More details can be found in article 10.1002/cbic.202400562 by Ken-Tye Yong, Tianxun Gong, Kien Voon Kong, and co-workers.<figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397179","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202580302
Isis M. Wahl, Kushal Sengupta, Maurice van Gastel, Laure Decamps, Serena DeBeer
{"title":"Cover Feature: Understanding the P-Cluster of Vanadium Nitrogenase: an EPR and XAS Study of the Holo vs. Apo Forms of the Enzyme (ChemBioChem 3/2025)","authors":"Isis M. Wahl, Kushal Sengupta, Maurice van Gastel, Laure Decamps, Serena DeBeer","doi":"10.1002/cbic.202580302","DOIUrl":"https://doi.org/10.1002/cbic.202580302","url":null,"abstract":"<p>The cover illustrates the structure of the P-cluster, one of the two Fe-S clusters present in the catalytic moiety of nitrogenase. The background illustration is the vanadium nitrogenase catalytic component (VFe), which is the focus of article 10.1002/cbic.202400833. In this work, Laure Decamps, Serena DeBeer, and co-workers combine biochemical, electron paramagnetic resonance (EPR) spectroscopy, and extended X-ray absorption fine structure (EXAFS) data to shed light on open questions about the structural differences between the holo and apo forms of VFe.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397187","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202500085
Ruiwen Xu, Jiawen Huang, Ariel J Kuhn, Samuel H Gellman
{"title":"Effects of D-Amino Acid Replacements on the Conformational Stability of Miniproteins.","authors":"Ruiwen Xu, Jiawen Huang, Ariel J Kuhn, Samuel H Gellman","doi":"10.1002/cbic.202500085","DOIUrl":"10.1002/cbic.202500085","url":null,"abstract":"<p><p>For many proteins, proper function requires adoption of a specific tertiary structure. This study explores the effects of L-to-D amino acid substitutions on tertiary structure stability for two well-known miniproteins, a single-site variant of the chicken villin headpiece subdomain (VHP) and the human Pin1 WW domain (WW). For VHP, which features an α-helix-rich tertiary structure, substitutions led to significant destabilization, as detected by variable temperature circular dichroism (CD) measurements. For WW, which has a β-sheet-rich tertiary structure, most single L-to-D changes seemed to cause complete unfolding at room temperature, according to CD measurements. These findings suggest that amino acid residue configuration changes at a single site will often prove to be deleterious in terms of tertiary structure stability, and in some cases dramatically destabilizing.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500085"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412589","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202580304
Flaminia Mancini, Hana Cahova
{"title":"Cover Feature: The Mysterious World of Non-Canonical Caps – What We Know and Why We Need New Sequencing Techniques (ChemBioChem 3/2025)","authors":"Flaminia Mancini, Hana Cahova","doi":"10.1002/cbic.202580304","DOIUrl":"https://doi.org/10.1002/cbic.202580304","url":null,"abstract":"<p>Dive into the intriguing world of 5’ non-canonical RNA caps —unique modifications derived from metabolites and cofactors such as NAD, FAD, CoA, UDP-glucose, UDP-N-acetylglucosamine, and dinucleoside polyphosphates—that challenge the long-held belief that RNA is capped solely by N7-methylguanosine. This review 10.1002/cbic.202400604 by Flaminia Mancini and Hana Cahova highlights how cutting-edge techniques like LC-MS have uncovered these caps across all domains of life and evaluates existing sequencing methods, emphasizing the urgent need for innovative technologies to decipher their biological roles. Discover a rapidly evolving field that could reshape our understanding of RNA biology.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202580304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396817","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202400943
Ngoc Anh Thu Ho, Fiona M Given, Tamsyn Stanborough, Michelle Klein, Timothy M Allison, Esther M M Bulloch, Wanting Jiao, Jodie M Johnston
{"title":"Apparent Reversal of Allosteric Response in Mycobacterium tuberculosis MenD Reveals Links to Half-of-Sites Reactivity.","authors":"Ngoc Anh Thu Ho, Fiona M Given, Tamsyn Stanborough, Michelle Klein, Timothy M Allison, Esther M M Bulloch, Wanting Jiao, Jodie M Johnston","doi":"10.1002/cbic.202400943","DOIUrl":"10.1002/cbic.202400943","url":null,"abstract":"<p><p>Redox-active molecules play critical roles in various biological functions, including cellular respiration. In bacterial electron transport chains, menaquinones serve as key electron carriers. The first committed enzyme in the menaquinone biosynthesis pathway of Mycobacterium tuberculosis (Mtb), MenD, is allosterically inhibited by 1,4-dihydroxy-2-naphthoic acid (DHNA), the first redox-active metabolite in the pathway. Structural asymmetries in Mtb-MenD suggest that this enzyme operates via a half-of-sites mechanism for catalysis. Here, we investigate the interplay between its catalytic and allosteric mechanisms. Using molecular dynamics (MD) simulations, mutagenesis, kinetic and binding assays, and structural analyses, we identified and characterised mutants of two residues, D141 and D306, involved in stabilising asymmetric conformations associated with allostery. These mutations had complex effects on Mtb-MenD's reaction kinetics, with the D306 mutants showing an apparent reversal of the allosteric response to DHNA. Our findings indicate that asymmetric active site conformations may facilitate optimal binding of cofactors and substrates, while the transition between alternating active site conformations is essential for the catalytic cycle. DHNA binding stabilises asymmetry in the tetramer, likely promoting the binding of cofactors, substrates, or reaction intermediates. However, DHNA interferes with the transition between alternating conformations, ultimately impairing turnover and catalytic cycling in Mtb-MenD.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400943"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404979","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}
ChemBioChemPub Date : 2025-02-13DOI: 10.1002/cbic.202400848
Mingchuan Mao, Yao Lei, Xianbin Ma, Hai-Yan Xie
{"title":"Challenges and Emerging Strategies of Immunotherapy for Glioblastoma.","authors":"Mingchuan Mao, Yao Lei, Xianbin Ma, Hai-Yan Xie","doi":"10.1002/cbic.202400848","DOIUrl":"10.1002/cbic.202400848","url":null,"abstract":"<p><p>Glioblastoma (GBM) is recognized as the most lethal primary malignant tumor of the central nervous system. Although traditional treatments can somewhat prolong patient survival, the overall prognosis remains grim. Immunotherapy has become an effective method for GBM treatment. Oncolytic virus, checkpoint inhibitors, CAR T cells and tumor vaccines have all been applied in this field. Moreover, the combining of immunotherapy with traditional radiotherapy, chemotherapy, or gene therapy can further improve the treatment outcome. This review systematically summarizes the features of GBM, the recent progress of immunotherapy in overcoming GBM.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400848"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404980","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}