Current Research in Structural Biology最新文献

{"title":"Structure of Helicobacter pylori dihydroneopterin aldolase suggests a fragment-based strategy for isozyme-specific inhibitor design","authors":"Gary X. Shaw ,&nbsp;Lixin Fan ,&nbsp;Scott Cherry ,&nbsp;Genbin Shi ,&nbsp;Joseph E. Tropea ,&nbsp;Xinhua Ji","doi":"10.1016/j.crstbi.2023.100095","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100095","url":null,"abstract":"<div><p>Dihydroneopterin aldolase (DHNA) is essential for folate biosynthesis in microorganisms. Without a counterpart in mammals, DHNA is an attractive target for antimicrobial agents. <em>Helicobacter pylori</em> infection occurs in human stomach of over 50% of the world population, but first-line therapies for the infection are facing rapidly increasing resistance. Novel antibiotics are urgently needed, toward which structural information on potential targets is critical. We have determined the crystal structure of <em>H. pylori</em> DHNA (HpDHNA) in complex with a pterin molecule (HpDHNA:Pterin) at 1.49-Å resolution. The HpDHNA:Pterin complex forms a tetramer in crystal. The tetramer is also observed in solution by dynamic light scattering and confirmed by small-angle X-ray scattering. To date, all but one reported DHNA structures are octameric complexes. As the only exception, ligand-free <em>Mycobacterium tuberculosis</em> DHNA (apo-MtDHNA) forms a tetramer in crystal, but its active sites are only partially formed. In contrast, the tetrameric HpDHNA:Pterin complex has well-formed active sites. Each active site accommodates one pterin molecule, but the exit of active site is blocked by two amino acid residues exhibiting a contact distance of 5.2 ​Å. In contrast, the corresponding contact distance in <em>Staphylococcus aureus</em> DHNA (SaDHNA) is twice the size, ranging from 9.8 to 10.5 ​Å, for ligand-free enzyme, the substrate complex, the product complex, and an inhibitor complex. This large contact distance indicates that the active site of SaDHNA is wide open. We propose that this isozyme-specific contact distance (ISCD) is a characteristic feature of DHNA active site. Comparative analysis of HpDHNA and SaDHNA structures suggests a fragment-based strategy for the development of isozyme-specific inhibitors.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100095"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cytosine-patch sequence motif identified in the conserved region of lincRNA-p21 interacts with the KH3 domain of hnRNPK","authors":"Aditi Maulik ,&nbsp;Devleena Bandopadhyay ,&nbsp;Mahavir Singh","doi":"10.1016/j.crstbi.2023.100099","DOIUrl":"10.1016/j.crstbi.2023.100099","url":null,"abstract":"<div><p>Long Intergenic Non-coding RNAs (lincRNAs) are the largest class of long non-coding RNAs in eukaryotes, originating from the genome's intergenic regions. A ∼4 ​kb long lincRNA-p21 is derived from a transcription unit next to the p21/Cdkn1a gene locus. LincRNA-p21 plays regulatory roles in p53-dependent transcriptional and translational repression through its physical association with proteins such as hnRNPK and HuR. It is also involved in the aberrant gene expression in different cancers. In this study, we have carried out a bioinformatics-based gene analysis and annotation of lincRNA-p21 to show that it is highly conserved in primates and identified two conserved domains in its sequence at the 5′ and 3′ terminal regions. hnRNPK has previously been shown to interact specifically with the 5′ conserved region of lincRNA-p21. hnRNPK is known to bind preferentially to the pyrimidine-rich (poly C) nucleotide sequences in RNAs. Interestingly, we observed a single occurrence of a cytosine-rich patch (C-patch) consisting of a CUCCCGC sequence in the 5′ conserved region of human lincRNA-p21, making it a putative hnRNPK binding motif. Using NMR and ITC experiments, we showed that the single-stranded C-patch containing RNA sequence motif interacts specifically with the KH3 domain of hnRNPK.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100099"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/41/main.PMC10023864.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9155549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural modelling and dynamics of full-length of TLR10 sheds light on possible modes of dimerization, ligand binding and mechanism of action","authors":"Vikas Tiwari,&nbsp;R. Sowdhamini","doi":"10.1016/j.crstbi.2023.100097","DOIUrl":"10.1016/j.crstbi.2023.100097","url":null,"abstract":"<div><p>Toll like receptors (TLRs) play a pivotal role in innate and adaptive immunity. There are 10 TLRs in the human genome, of which TLR10 is the least characterized. Genetic polymorphism of TLR10 has been shown to be associated with multiple diseases including tuberculosis and rheumatoid arthritis. TLR10 consists of an extracellular domain (ECD), a single-pass transmembrane (TM) helix and intracellular TIR (Toll/Interleukin-1 receptor) domain. ECD is employed for ligand recognition and the intracellular domain interacts with other TIR domain-containing adapter proteins for signal transduction. Experimental structure of ECD or TM domain is not available for TLR10. In this study, we have modelled multiple forms of TLR10-ECD dimers, such as closed and open forms, starting from available structures of homologues. Subsequently, multiple full-length TLR10 homodimer models were generated by utilizing homology modelling and protein-protein docking. The dynamics of these models in membrane-aqueous environment revealed the global motion of ECD and TIR domain towards membrane bilayer. The TIR domain residues exhibited high root mean square fluctuation compared to ECD. The ‘closed form’ model was observed to be energetically more favorable than ‘open form’ model. The evaluation of persistent interchain interactions, along with their conservation score, unveiled critical residues for each model. Further, the binding of dsRNA to TLR10 was modelled by defined and blind docking approaches. Differential binding of dsRNA to the protomers of TLR10 was observed upon simulation that could provide clues on ligand disassociation. Dynamic network analysis revealed that the ‘open form’ model can be the functional form while ‘closed form’ model can be the apo form of TLR10.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100097"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/2e/main.PMC9996232.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing large-scale production of TEV protease through an innovative NT* tag-based fusion construct","authors":"Pragyan P. Parida,&nbsp;Deepa Saraswathi,&nbsp;Subbarao M.V. Mopidevi,&nbsp;Sreejith Raran-Kurussi","doi":"10.1016/j.crstbi.2023.100106","DOIUrl":"10.1016/j.crstbi.2023.100106","url":null,"abstract":"<div><p>Tobacco etch virus Protease (TEVp), a cysteine protease, is renowned for its remarkable specific proteolysis, making it an invaluable tool for removing fusion tags from recombinant proteins. However, TEV protease's inherent insolubility limits its broad application. Fusion constructs like an N-terminal MBP fusion, known for its improved solubility, have been employed for TEVp production to address this issue. In this study, we fused the TEVp with the N-terminal domain of the spider silk protein, specifically utilizing a charge-reversed mutant (D40K/K65D) of the N-terminal domain of major ampullate spidroin-1 protein from <em>Euprosthenops australis</em>, referred to as NT*. This fusion construct contains a TEVp cleavage site, enabling intracellular self-processing and the release of a His₇-tagged protease. The significant increase in soluble protein expression allowed us to purify approximately 90–100 mg of TEVp from a 1-L <em>E. coli</em> culture, surpassing previous findings by a considerable margin. The enzyme remained stable and catalytically active even after several months of storage in a deep freezer (−80 °C).</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"6 ","pages":"Article 100106"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/23/main.PMC10563009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the versatility of human serum albumin – A comprehensive review of its biological significance and therapeutic potential","authors":"Sajda Ashraf ,&nbsp;Hina Qaiser ,&nbsp;Sumayya Tariq ,&nbsp;Asaad Khalid ,&nbsp;Hafiz A. Makeen ,&nbsp;Hassan A. Alhazmi ,&nbsp;Zaheer Ul-Haq","doi":"10.1016/j.crstbi.2023.100114","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100114","url":null,"abstract":"<div><p>Human serum albumin (HSA) is a multi-domain macromolecule with diverse ligand binding capability because of its ability to allow allosteric modulation despite being a monomeric protein. Physiologically, HSA act as the primary carrier for various exogenous and endogenous compounds and fatty acids, and alter the pharmacokinetic properties of several drugs. It has antioxidant properties and is utilized therapeutically to improve the drug delivery of pharmacological agents for the treatment of several disorders. The flexibility of albumin in holding various types of drugs coupled with a variety of modifications makes this protein a versatile drug carrier with incalculable potential in therapeutics. This review provides a brief outline of the different structural properties of HSA, and its various binding sites, moreover, an overview of the genetic, biomedical, and allosteric modulation of drugs and drug delivery aspects of HSA is also included, which may be helpful in guiding advanced clinical applications and further research on the therapeutic potential of this extraordinary protein.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"6 ","pages":"Article 100114"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X2300020X/pdfft?md5=b48d75ec4e200dc2416c06c820ca16bf&pid=1-s2.0-S2665928X2300020X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138501233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural rationale to understand the effect of disease-associated mutations on Myotubularin","authors":"Teerna Bhattacharyya ,&nbsp;Avishek Ghosh ,&nbsp;Shailya Verma,&nbsp;Padinjat Raghu,&nbsp;Ramanathan Sowdhamini","doi":"10.1016/j.crstbi.2023.100100","DOIUrl":"10.1016/j.crstbi.2023.100100","url":null,"abstract":"<div><p>Myotubularin or MTM1 is a lipid phosphatase that regulates vesicular trafficking in the cell. The <em>MTM1</em> gene is mutated in a severe form of muscular disease, X-linked myotubular myopathy or XLMTM, affecting 1 in 50,000 newborn males worldwide. There have been several studies on the disease pathology of XLMTM, but the structural effects of missense mutations of MTM1 are underexplored due to the unavailability of a crystal structure. MTM1 consists of three domains-a lipid-binding N-terminal GRAM domain, the phosphatase domain and a coiled-coil domain which aids dimerisation of Myotubularin homologs. While most mutations reported to date map to the phosphatase domain of MTM1, the other two domains on the sequence are also frequently mutated in XLMTM. To understand the overall structural and functional effects of missense mutations on MTM1, we curated several missense mutations and performed <em>in silico</em> and <em>in vitro</em> studies. Apart from significantly impaired binding to substrate, abrogation of phosphatase activity was observed for a few mutants. Possible long-range effects of mutations from non-catalytic domains on phosphatase activity were observed as well. Coiled-coil domain mutants have been characterised here for the first time in XLMTM literature.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100100"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123148/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and prioritization of potential therapeutic molecules against LpxA from Acinetobacter baumannii – A computational study","authors":"Rameez Jabeer Khan ,&nbsp;Ekampreet Singh ,&nbsp;Rajat Kumar Jha ,&nbsp;Ankit Kumar ,&nbsp;Saurabh Kumar Bhati ,&nbsp;Mahrukh Parveez Zia ,&nbsp;Monika Jain ,&nbsp;Rashmi Prabha Singh ,&nbsp;Jayaraman Muthukumaran ,&nbsp;Amit Kumar Singh","doi":"10.1016/j.crstbi.2023.100096","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100096","url":null,"abstract":"<div><p>A. baumannii is a ubiquitously found gram-negative, multi-drug resistant bacterial species from the ESKAPE family of pathogens known to be the causative agent for hospital-acquired infections such as pneumonia, meningitis, endocarditis, septicaemia and urinary tract infections. <em>A. baumannii</em> is implicated as a contributor to bloodstream infections in approximately 2% of all worldwide infections. Hence, exploring novel therapeutic agents against the bacterium is essential. LpxA or UDP-<em>N</em>-acetylglucosamine acetyltransferase is an essential enzyme important in Lipid A biosynthesis which catalyses the reversible transfer of an acetyl group on the glucosamine 3-OH of the UDP-GlcNAc which is a crucial step in the biosynthesis of the protective Lipopolysaccharides (LPS) layer of the bacteria which upon disruption can lead to the elimination of the bacterium which delineates LpxA as an appreciable drug target from <em>A. baumannii</em>. The present study performs high throughput virtual screening of LpxA against the enamine-HTSC-large-molecule library and performs toxicity and ADME screening to identify the three promising lead molecules subjected to molecular dynamics simulations. Global and essential dynamics analysis of LpxA and its complexes along with FEL and MM/PBSA based binding free energy delineate Z367461724 and Z219244584 as potential inhibitors against LpxA from <em>A. baumannii</em>.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100096"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure of the Saccharolobus solfataricus type III-D CRISPR effector","authors":"Giuseppe Cannone ,&nbsp;Dmytro Kompaniiets ,&nbsp;Shirley Graham ,&nbsp;Malcolm F. White ,&nbsp;Laura Spagnolo","doi":"10.1016/j.crstbi.2023.100098","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100098","url":null,"abstract":"<div><p>CRISPR-Cas is a prokaryotic adaptive immune system, classified into six different types, each characterised by a signature protein. Type III systems, classified based on the presence of a Cas10 subunit, are rather diverse multi-subunit assemblies with a range of enzymatic activities and downstream ancillary effectors. The broad array of current biotechnological CRISPR applications is mainly based on proteins classified as Type II, however recent developments established the feasibility and efficacy of multi-protein Type III CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes. The crenarchaeon <em>Saccharolobus solfataricus</em> has two type III system subtypes (III–B and III-D). Here, we report the cryo-EM structure of the Csm Type III-D complex from <em>S. solfataricus</em> (SsoCsm), which uses CRISPR RNA to bind target RNA molecules, activating the Cas10 subunit for antiviral defence. The structure reveals the complex organisation, subunit/subunit connectivity and protein/guide RNA interactions of the SsoCsm complex, one of the largest CRISPR effectors known.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"5 ","pages":"Article 100098"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49813935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taking stock of the mutations in human SARS-CoV-2 spike proteins: From early days to nearly the end of COVID-19 pandemic","authors":"Lalitha Guruprasad,&nbsp;Gatta KRS. Naresh,&nbsp;Ganesh Boggarapu","doi":"10.1016/j.crstbi.2023.100107","DOIUrl":"10.1016/j.crstbi.2023.100107","url":null,"abstract":"<div><p>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causative agent of the coronavirus disease-2019 (COVID-19) has resulted in several deaths and severe economic losses throughout the world. The spike protein in the virus binds to the human ACE-2 receptor in order to mediate virus-host interactions required for the viral transmission. Since first report of the SARS-CoV-2 sequence during December 2019 from patient infected with the virus in Wuhan, China, the virus has undergone rapid changes leading to mutations comprising substitutions, deletions and insertions in the sequence resulting in several variants of the virus that were more virulent and transmissible or less virulent but highly transmissible. The timely intervention with COVID-19 vaccines proved to be effective in controlling the number of infections. However, rapid mutations in the virus led to the lowering of vaccine efficacies being administered to people. In May 2023, the World Health Organization declared COVID-19 was not a public health emergency of international concern anymore. In order to take stock of mutations in the virus from early days to nearly end of COVID-19 pandemic, sequence analyses of the SARS-CoV-2 spike proteins available in the NCBI Virus database was carried out. The mutations and invariant residues in the SARS-CoV-2 spike protein sequences relative to the reference sequence were analysed. The location of the invariant residues and residues at interface of the protein chains in the spike protein trimer complex structure were examined. A total of 111,298 non-redundant SARS-CoV-2 spike protein sequences representing 2,345,585 spike proteins in the NCBI Virus database showed mutations at 1252 of the 1273 positions in the amino acid sequence. The mutations represented 6129 different mutation types in the sequences analysed. Besides, some sequences also contained insertion mutations. The SARS-CoV-2 spike protein sequences represented 1435 lineages. In addition, several spike protein sequences with mutations whose lineages were either ‘not classified’ or were ‘unclassifiable’ indicated the virus could still be evolving.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"6 ","pages":"Article 100107"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/f8/main.PMC10569959.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel peptide inhibitors targeting CD40 and CD40L interaction: A potential for atherosclerosis therapy","authors":"Kundan Solanki ,&nbsp;Ashutosh Kumar ,&nbsp;Mohd Shahnawaz Khan ,&nbsp;Subramani Karthikeyan ,&nbsp;Rajat Atre ,&nbsp;Kam Y.J. Zhang ,&nbsp;Evgeny Bezsonov ,&nbsp;Alexander G. Obukhov ,&nbsp;Mirza S. Baig","doi":"10.1016/j.crstbi.2023.100110","DOIUrl":"10.1016/j.crstbi.2023.100110","url":null,"abstract":"<div><p>Atherosclerosis is a chronic inflammatory disease characterized by plaque build-up in the arteries, leading to the obstruction of blood flow. Macrophages are the primary immune cells found in the atherosclerotic lesions and are directly involved in atherosclerosis progression. Macrophages are derived from extravasating blood monocytes. The monocytic CD40 receptor is important for monocyte recruitment on the endothelium expressing the CD40 ligand (CD40L). Thus, targeting monocyte/macrophage interaction with the endothelium by inhibiting CD40-CD40L interaction may be a promising strategy for attenuating atherosclerosis. Monoclonal antibodies have been used against this target but shows various complications. We used an array of computer-aided drug discovery tools and molecular docking approaches to design a therapeutic inhibitory peptide that could efficiently bind to the critical residues (82Y, 84D, and 86N) on the CD40 receptor essential for the receptor's binding to CD40L. The initial screen identified a parent peptide with a high binding affinity to CD40, but the peptide exhibited a positive hepatotoxicity score. We then designed several novel peptidomimetic derivatives with higher binding affinities to CD40, good physicochemical properties, and negative hepatotoxicity as compared to the parent peptide. Furthermore, we conducted molecular dynamics simulations for both the apo and complexed forms of the receptor with ligand, and screened peptides to evaluate their stability. The designed peptidomimetic derivatives are promising therapeutics targeting the CD40-CD40L interaction and may potentially be used to attenuate atherosclerosis.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"6 ","pages":"Article 100110"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X23000168/pdfft?md5=dfb0a3b830f516c5107d4d908c6fc166&pid=1-s2.0-S2665928X23000168-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135763363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}