{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:52:09Z","timestamp":1770270729266,"version":"3.49.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The <jats:italic>Staphylococcus aureus<\/jats:italic> exfoliative toxins (ETs) are the main toxins that produce staphylococcal scalded skin syndrome (SSSS), an abscess skin disorder. The victims of the disease are usually newborns and kids, as well as grown-up people. Five ETs namely, exfoliative toxins A, B, C, D, and E have been identified in <jats:italic>S. aureus<\/jats:italic>. The three-dimensional (3D) structure of exfoliative toxins A, B, C and E is known, while that of exfoliative toxin D (ETD) is still unknown. In this work, we have predicted the 3D structure of ETD using protein modeling techniques (software used for 3D structure modeling comprising the MODELLER 9v19 program, SWISS-Model, and I-TESSER). The validation of the build model was done using PROCHECK (Ramachandran plot), ERRAT2, and Verify 3D programs. The results from 3D modeling show that the build model was of good quality as indicated by a GMQE score of 0.88 and by 91.1% amino acid residues in the most favored region of the Ramachandran plot, the ERRAT2 quality factor of 90.1%, and a verify3D score of &amp;gt;0.2 for 99.59% of amino acid residues. The 3D structure analysis indicates that the overall structure of ETD is similar to the chymotrypsin-like serine protease fold. The structure is composed of 13 \u03b2-strands and seven \u03b1-helices that fold into two well-defined six-strand \u03b2-barrels whose axes are roughly perpendicular to each other. The active site residues include histidine-97, aspartic acid-147, and serine-221. This represents the first structure report of ETD. Structural comparison with the other ETs shows some differences, particularly in the loop region, which also change the overall surface charge of these toxins. This may convey variable substrate specificity to these toxins. The inhibition of these toxins by natural (2S albumin and flocculating proteins from <jats:italic>Moringa oleifera<\/jats:italic> seeds) and synthetic inhibitors (suramin) was also carried out in this study. The results from docking indicate that the inhibitors bind near the C-terminal domain which may restrict the movement of this domain and may halt the access of the substrate to the active site of this enzyme. Molecular dynamic simulation was performed to see the effect of inhibitor binding to the enzyme. This work will further elucidate the structure\u2013function relationship of this enzyme. The inhibition of this enzyme will lead to a new treatment for SSSS.<\/jats:p>","DOI":"10.3389\/fphar.2022.800970","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T10:09:20Z","timestamp":1645178960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Three-Dimensional Structure Characterization and Inhibition Study of Exfoliative Toxin D From Staphylococcus aureus"],"prefix":"10.3389","volume":"13","author":[{"given":"Anwar","family":"Ullah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajmal","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Al-Harrasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kifayat","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asghar","family":"Shabbir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","first-page":"372","article-title":"Abscess of the Nasal Septum with Staphylococcal Scalded Skin Syndrome","volume":"43","author":"Adhisivam","year":"2006","journal-title":"Indian Pediatr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/81385","article-title":"Toxin in Bullous Impetigo and Staphylococcal Scalded-Skin Syndrome Targets Desmoglein 1","volume":"6","author":"Amagai","year":"2000","journal-title":"Nat. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1046\/j.1523-1747.2002.01751.x","article-title":"Staphylococcal Exfoliative Toxin B Specifically Cleaves Desmoglein 1","volume":"118","author":"Amagai","year":"2002","journal-title":"J. Invest. Dermatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"W537","DOI":"10.1093\/nar\/gks375","article-title":"H++ 3.0: Automating pK Prediction and the Preparation of Biomolecular Structures for Atomistic Molecular Modeling and Simulations","volume":"40","author":"Anandakrishnan","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/s0021-9258(18)64384-4","article-title":"Reactivity and Catalysis in Reactions of the Serine Hydroxyl Group and of O-Acyl Serines","volume":"236","author":"Anderson","year":"1961","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"663831","DOI":"10.3389\/fmicb.2021.663831","article-title":"Genomic Epidemiology and Global Population Structure of Exfoliative Toxin A-Producing Staphylococcus aureus Strains Associated with Staphylococcal Scalded Skin Syndrome","volume":"12","author":"Azarian","year":"2021","journal-title":"Front. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S1359-0278(96)00052-1","article-title":"Conserved Features in the Active Site of Nonhomologous Serine Proteases","volume":"1","author":"Bagley","year":"1996","journal-title":"Fold Des"},{"key":"B8","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jmb.2004.05.028","article-title":"Improved Prediction of Signal Peptides: SignalP 3.0","volume":"340","author":"Bendtsen","year":"2004","journal-title":"J. Mol. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-e","article-title":"GROMACS: A Message-Passing Parallel Molecular Dynamics Implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comp. Phys. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1093\/nar\/gkh580","article-title":"Predicting Transmembrane Beta-Barrels in Proteomes","volume":"32","author":"Bigelow","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.1021\/bi00665a023","article-title":"A Detailed Structural Comparison between the Charge Relay System in Chymotrypsinogen and in Alpha-Chymotrypsin","volume":"15","author":"Birktoft","year":"1976","journal-title":"Biochemistry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1126\/science.1853201","article-title":"A Method to Identify Protein Sequences that Fold into a Known Three-Dimensional Structure","volume":"253","author":"Bowie","year":"1991","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/s0969-2126(97)00235-9","article-title":"The Structure of Staphylococcus aureus Epidermolytic Toxin A, an Atypic Serine Protease, at 1.7 A Resolution","volume":"5","author":"Cavarelli","year":"1997","journal-title":"Structure"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of Protein Structures: Patterns of Nonbonded Atomic Interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/s0190-9622(94)70032-x","article-title":"Staphylococcal Scalded Skin Syndrome in Adults. A Clinical Review Illustrated with a New Case","volume":"30","author":"Cribier","year":"1984","journal-title":"J. Am. Acad. Dermatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: A Sequence Logo Generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N log (N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"B17","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/s0076-6879(88)65049-x","article-title":"Assays for Epidermolytic Toxin of Staphylococcus aureus","volume":"165","author":"De Azavedo","year":"1988","journal-title":"Methods Enzymol."},{"key":"B18","volume-title":"The PyMOL Molecular Graphics System","author":"De Lano","year":"2002"},{"key":"B19","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1179\/acb.2004.053","article-title":"Staphyloccocal Scalded Skin Syndrome in an Adult","volume":"59","author":"Decleire","year":"2004","journal-title":"Acta Clin. Belg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"adv00110","DOI":"10.2340\/00015555-3466","article-title":"Skin Infections Caused by Staphylococcus aureus","volume":"100","author":"Del Giudice","year":"2020","journal-title":"Acta Derm Venereol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"26932","DOI":"10.1039\/c5ra03063c","article-title":"Insights into the C-H\u22efF-C Hydrogen Bond by Cambridge Structural Database Analyses and Computational Studies","volume":"5","author":"Dev","year":"2015","journal-title":"RSC Adv."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1021\/ja00299a024","article-title":"Development and Use of Quantum Mechanical Molecular Models. 76. AM1: a New General Purpose Quantum Mechanical Molecular Model","volume":"107","author":"Dewar","year":"1985","journal-title":"J. Am. Chem. Soc."},{"key":"B23","doi-asserted-by":"publisher","first-page":"W665","DOI":"10.1093\/nar\/gkh381","article-title":"PDB2PQR: an Automated Pipeline for the Setup of Poisson-Boltzmann Electrostatics Calculations","volume":"32","author":"Dolinsky","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jiac.2021.07.013","article-title":"Methicillin-resistant Staphylococcus aureus Transmission and Hospital-Acquired Bacteremia in a Neonatal Intensive Care Unit in Greece","author":"Doudoulakakis","year":"2021","journal-title":"J. Infect. Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.toxicon.2007.01.002","article-title":"Suramin Counteracts the Haemostatic Disturbances Produced by Bothrops jararaca Snake Venom","volume":"49","author":"Fernandes","year":"2007","journal-title":"Toxicon"},{"key":"B26","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1107\/S0907444910020081","article-title":"Structure of Staphylococcus aureus Adenylosuccinate Lyase (PurB) and Assessment of its Potential as a Target for Structure-Based Inhibitor Discovery","volume":"66","author":"Fyfe","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"537","DOI":"10.3390\/toxins12090537","article-title":"Staphylococcus aureus Exotoxins and Their Detection in the Dairy Industry and Mastitis","volume":"12","author":"G Abril","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B28","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","article-title":"Protein Identification and Analysis Tools on the ExPASy Server","volume-title":"The Proteomics Protocols Handbook","author":"Gasteiger","year":"2005"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1101\/gr.278202","article-title":"CDART: Protein Homology by Domain Architecture","volume":"12","author":"Geer","year":"2002","journal-title":"Genome Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1099\/00222615-43-5-318","article-title":"Staphylococcal Scalded Skin Syndrome","volume":"43","author":"Gemmell","year":"1997","journal-title":"J. Med. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"632","DOI":"10.2174\/092986607781483831","article-title":"ParDOCK: An All Atom Energy Based Monte Carlo Docking Protocol for Protein-Ligand Complexes","volume":"14","author":"Gupta","year":"2007","journal-title":"Protein Pept. Lett."},{"key":"B32","unstructured":"Prediction of N-Glycosylation Sites in Human Proteins\n            GuptaR.\n            JungE.\n            BrunakS.\n          2004"},{"key":"B108","doi-asserted-by":"publisher","first-page":"53-60","DOI":"10.1172\/JCI15766","article-title":"Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome","volume":"110","author":"Hanakawa","year":"2002","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1046\/j.1523-1747.2003.12362.x","article-title":"Calcium-dependent Conformation of Desmoglein 1 Is Required for its Cleavage by Exfoliative Toxin","volume":"121","author":"Hanakawa","year":"2003","journal-title":"J. Invest. Dermatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1093\/jb\/mvh182","article-title":"Mechanisms of Blister Formation by Staphylococcal Toxins","volume":"136","author":"Hanakawa","year":"2004","journal-title":"J. Biochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1042\/bj0560288","article-title":"The Reaction of P-Nitrophenyl Esters with Chymotrypsin and Insulin","volume":"56","author":"Hartley","year":"1954","journal-title":"Biochem. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1089\/mdr.2018.0333","article-title":"Prevalence and Genetic Characteristics of Methicillin-ResistantStaphylococcus Aureusand Coagulase-Negative Staphylococci Isolated from Oral Cavity of Healthy Children in Japan","volume":"25","author":"Hirose","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1093\/bioinformatics\/bts139","article-title":"MDWeb and MDMoby: An Integrated Web-Based Platform for Molecular Dynamics Simulations","volume":"28","author":"Hospital","year":"2012","journal-title":"Bioinformatics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3694","DOI":"10.1093\/bioinformatics\/btw637","article-title":"Recognizing Metal and Acid Radical Ion-Binding Sites by Integrating Ab Initio Modeling with Template-Based Transferals","volume":"32","author":"Hu","year":"2016","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2133.2011.10515.x","article-title":"Mild Staphylococcal Scalded Skin Syndrome: an Underdiagnosed Clinical Disorder","volume":"166","author":"Hubiche","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph"},{"key":"B107","doi-asserted-by":"publisher","first-page":"16336","DOI":"10.1038\/s41598-019-52777-3","article-title":"Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity","volume":"9","author":"Imanishi","year":"1996","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1002\/jcc.10128","article-title":"Fast, Efficient Generation of High-Quality Atomic Charges. AM1-BCC Model: II. Parameterization and Validation","volume":"23","author":"Jakalian","year":"2002","journal-title":"J. Comput. Chem."},{"key":"B42","volume-title":"An Introduction to Hydrogen Bonding","author":"Jeffrey","year":"1997"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.1128\/JVI.00672-13","article-title":"Structure of Severe Fever with Thrombocytopenia Syndrome Virus Nucleocapsid Protein in Complex with Suramin Reveals Therapeutic Potential","volume":"87","author":"Jiao","year":"2013","journal-title":"J. Virol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1007\/s12098-009-0212-0","article-title":"Staphylococcal Scalded Skin Syndrome in a Neonate","volume":"76","author":"Kadam","year":"2009","journal-title":"Indian J. Pediatr."},{"key":"B45","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1111\/j.1440-1754.2008.01316.x","article-title":"Staphylococcal Scalded Skin Syndrome in an Extremely Premature Neonate: a Case Report with a Brief Review of Literature","volume":"44","author":"Kapoor","year":"2008","journal-title":"J. Paediatr. Child. Health"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1006\/jmbi.2001.5305","article-title":"Crystal Structure Reveals Basis for the Inhibitor Resistance of Human Brain Trypsin","volume":"315","author":"Katona","year":"2002","journal-title":"J. Mol. Biol."},{"key":"B47","first-page":"715","volume-title":"Staphylococcal Infections","author":"Kimberlin","year":"2015"},{"key":"B48","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1128\/CMR.12.2.224","article-title":"Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins Causing Staphylococcal Scalded-Skin Syndrome","volume":"12","author":"Ladhani","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1097\/00006454-200006000-00021","article-title":"Familial Outbreak of Staphylococcal Scalded Skin Syndrome","volume":"19","author":"Ladhani","year":"2000","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B50","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0928-8244(03)00225-6","article-title":"Understanding the Mechanism of Action of the Exfoliative Toxins of Staphylococcus aureus","volume":"39","author":"Ladhani","year":"2003","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1107\/s0021889892009944","article-title":"PROCHECK: A Program to Check the Stereochemical Quality of Protein Structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Cryst."},{"key":"B52","first-page":"722","article-title":"PROCHECK: Validation of Protein Structure Coordinates","volume-title":"International Tables of Crystallography: Volume F: Crystallography of Biological Macromolecules","author":"Laskowski","year":"2001"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3389\/fmicb.2020.01057","article-title":"An Enhanced Variant Designed from DLP4 Cationic Peptide against Staphylococcus aureus CVCC 546","volume":"11","author":"Li","year":"2020","journal-title":"Front. Microbiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.bbapap.2009.03.011","article-title":"Structural and Thermodynamic Analysis of Thrombin:suramin Interaction in Solution and crystal Phases","volume":"1794","author":"Lima","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B55","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/356083a0","article-title":"Assessment of Protein Models with Three-Dimensional Profiles","volume":"356","author":"L\u00fcthy","year":"1992","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/j.1365-2133.1979.tb03571.x","article-title":"Toxic Epidermal Necrolysis (The Scalded Skin Syndrome): a Reappraisal","volume":"100","author":"Lyell","year":"1979","journal-title":"Br. J. Dermatol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"638598","DOI":"10.3389\/fcimb.2021.638598","article-title":"The Pharmacodynamics Study of Insect Defensin DLP4 against Toxigenic Staphylococcus Hyicus ACCC 61734 In Vitro and Vivo","volume":"11","author":"Ma","year":"2021","journal-title":"Front. Cel Infect. Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theor. Comput."},{"key":"B59","doi-asserted-by":"publisher","first-page":"105655","DOI":"10.1016\/j.tvjl.2021.105655","article-title":"Porcine Ear Necrosis","volume":"271","author":"Malik","year":"2021","journal-title":"Vet. J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1089\/mdr.2019.0319","article-title":"Phenotype and Genotype Characteristics of Staphylococcus aureus Resistant to Methicillin\/Oxacillin Carrying Gene mecC in the Czech Republic from 2002 to 2017","volume":"26","author":"Mali\u0161ov\u00e1","year":"2020","journal-title":"Microb. Drug Resist."},{"key":"B61","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/pde.14032","article-title":"Disseminated Bullous Impetigo and Atopic Dermatitis: Case Series and Literature Review","volume":"37","author":"Mannschreck","year":"2020","journal-title":"Pediatr. Dermatol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1093\/nar\/gkw1129","article-title":"CDD\/SPARCLE: Functional Classification of Proteins via Subfamily Domain Architectures","volume":"45","author":"Marchler-Bauer","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.bbrc.2015.08.083","article-title":"Crystal Structure of Staphylococcus aureus Exfoliative Toxin D-like Protein: Structural Basis for the High Specificity of Exfoliative Toxins","volume":"467","author":"Mariutti","year":"2015","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B64","doi-asserted-by":"publisher","first-page":"W229","DOI":"10.1093\/nar\/gkn186","article-title":"FireDock: a Web Server for Fast Interaction Refinement in Molecular Docking","volume":"36","author":"Mashiach","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jmb.2012.03.008","article-title":"Structure-based Inhibition of Norovirus RNA-dependent RNA Polymerases","volume":"419","author":"Mastrangelo","year":"2012","journal-title":"J. Mol. Biol."},{"key":"B66","first-page":"101","article-title":"Staphylococci, Streptococci and the Skin: Review of Impetigo and Staphylococcal Scalded Skin Syndrome","volume":"1","author":"Melish","year":"1982","journal-title":"Semin. Dermatol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"531","DOI":"10.2174\/1871526519666190207092307","article-title":"Molecular Binding and Simulation Studies of Staphylococcus aureus Superantigens with Flavonoid Compounds","volume":"20","author":"Mohan","year":"2020","journal-title":"Infect. Disord. Drug Targets"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1016\/j.biocel.2004.03.007","article-title":"Suramin Interaction with Human Alpha-Thrombin: Inhibitory Effects and Binding Studies","volume":"36","author":"Monteiro","year":"2004","journal-title":"Int. J. Biochem. Cel Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"31232","DOI":"10.1074\/jbc.M110.212613","article-title":"The Trypanocidal Drug Suramin and Other Trypan Blue Mimetics Are Inhibitors of Pyruvate Kinases and Bind to the Adenosine Site","volume":"286","author":"Morgan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.jmb.2005.04.072","article-title":"Inhibition of Myotoxic Activity of Bothrops asper Myotoxin II by the Anti-trypanosomal Drug Suramin","volume":"350","author":"Murakami","year":"2005","journal-title":"J. Mol. Biol."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1097\/PEC.0000000000002564","article-title":"Recognizing and Managing Staphylococcal Scalded Skin Syndrome in the Emergency Department","author":"Nguyen","year":"2021","journal-title":"Pediatr. Emerg. Care"},{"key":"B73","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1159\/000245958","article-title":"Staphylococcal Scalded Skin Syndrome in an Adult","volume":"195","author":"Oono","year":"1997","journal-title":"Dermatology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1110\/ps.9.3.610","article-title":"Structural Similarities and Differences in Staphylococcus aureus Exfoliative Toxins A and B as Revealed by Their crystal Structures","volume":"9","author":"Papageorgiou","year":"2000","journal-title":"Protein Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1089\/mdr.2013.0153","article-title":"Detection and Genetic Characterization of PVL-Positive ST8-MRSA-IVa and Exfoliative Toxin D-Positive European CA-MRSA-Like ST1931 (CC80) MRSA-IVa Strains in Bangladesh","volume":"20","author":"Paul","year":"2014","journal-title":"Microb. Drug Resist."},{"key":"B76","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1002\/pro.5560040301","article-title":"Structural Basis of Substrate Specificity in the Serine Proteases","volume":"4","author":"Perona","year":"1995","journal-title":"Protein Sci."},{"key":"B77","doi-asserted-by":"crossref","first-page":"245e249","DOI":"10.1111\/j.1574-6968.1986.tb01703.x","article-title":"Fluorescence Studies Stability of Staphylococcal Exfoliative Toxins A and B","volume":"36","author":"Piemont","year":"1986","journal-title":"FEMS Microbiol. Lett."},{"key":"B78","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0022-5193(71)90130-5","article-title":"On the Mechanism of Proton Transfer in the Catalysis by Serine Proteases","volume":"31","author":"Polg\u00e1r","year":"1971","journal-title":"J. Theor. Biol."},{"key":"B79","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1073\/pnas.64.4.1335","article-title":"The Nature of General Base-General Acid Catalysis in Serine Proteases","volume":"64","author":"Polg\u00e1r","year":"1969","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B80","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1107\/s090744490302599x","article-title":"The Structure of a Universally Employed Enzyme: V8 Protease fromStaphylococcus Aureus","volume":"60","author":"Prasad","year":"2004","journal-title":"Acta Crystallogr. D Biol. Cryst."},{"key":"B81","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1093\/bioinformatics\/btx417","article-title":"SCooP: an Accurate and Fast Predictor of Protein Stability Curves as a Function of Temperature","volume":"33","author":"Pucci","year":"2017","journal-title":"Bioinformatics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1111\/j.1742-4658.2005.04604.x","article-title":"Short Hydrogen Bonds in Proteins","volume":"272","author":"Rajagopal","year":"2005","journal-title":"FEBS J."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1128\/iai.10.6.1260-1265.1974","article-title":"Interaction of Staphylococcal Exfoliative Toxin with Concanavalin A","volume":"10","author":"Rogolsky","year":"1974","journal-title":"Infect. Immun."},{"key":"B84","doi-asserted-by":"publisher","first-page":"W321","DOI":"10.1093\/nar\/gkh377","article-title":"The PredictProtein Server","volume":"32","author":"Rost","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: A Unified Platform for Automated Protein Structure and Function Prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat. Protoc."},{"key":"B86","doi-asserted-by":"publisher","first-page":"e0245351","DOI":"10.1371\/journal.pone.0245351","article-title":"Whole Genome Sequencing of Coagulase Positive Staphylococci from a Dog-And-Owner Screening Survey","volume":"16","author":"Sahin-T\u00f3th","year":"2021","journal-title":"PLoS One"},{"key":"B87","doi-asserted-by":"publisher","first-page":"10317","DOI":"10.1038\/s41598-018-28584-7","article-title":"Structural and Functional Characterization of Suramin-Bound MjTX-I from Bothrops Moojeni Suggests a Particular Myotoxic Mechanism","volume":"8","author":"Salvador","year":"2018","journal-title":"Sci. Rep."},{"key":"B88","doi-asserted-by":"publisher","first-page":"3780","DOI":"10.1128\/iai.62.9.3780-3785.1994","article-title":"A New Type of Staphylococcal Exfoliative Toxin from a Staphylococcus aureus Strain Isolated from a Horse with Phlegmon","volume":"62","author":"Sato","year":"1994","journal-title":"Infect. Immun."},{"key":"B89","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.1093\/nar\/18.20.6097","article-title":"Sequence Logos: A New Way to Display Consensus Sequences","volume":"18","author":"Schneider","year":"1990","journal-title":"Nucl. Acids Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: Servers for Rigid and Symmetric Docking","volume":"33","author":"Schneidman-Duhovny","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"840","DOI":"10.3390\/antibiotics10070840","article-title":"Exudative Epidermitis in Combination with Staphylococcal Pyoderma in Suckling Piglets","volume":"10","author":"Schwarz","year":"2021","journal-title":"Antibiotics"},{"key":"B92","first-page":"223","article-title":"Staphylococcal Scalded Skin Syndrome in an Immunocompetent Adult: Possible Implication of Low-Dosage Prednisone","volume":"62","author":"Shirin","year":"1998","journal-title":"Cutis"},{"key":"B93","doi-asserted-by":"publisher","first-page":"103692","DOI":"10.1016\/j.jprot.2020.103692","article-title":"Mo-HLPs: New Flocculating Agents Identified from Moringa Oleifera Seeds Belong to the Hevein-like Peptide Family","volume":"217","author":"Sousa","year":"2020","journal-title":"J. Proteomics"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1038\/emboj.2013.79","article-title":"Precision Mapping of the Human O-GalNAc Glycoproteome through SimpleCell Technology","volume":"32","author":"Steentoft","year":"2013","journal-title":"EMBO J."},{"key":"B95","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1146\/annurev.bb.11.060182.002223","article-title":"Crystallographic and NMR Studies of the Serine Proteases","volume":"11","author":"Steitz","year":"1982","journal-title":"Annu. Rev. Biophys. Bioeng."},{"key":"B96","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.bbrc.2015.10.087","article-title":"Crystal structure of mature 2S albumin from Moringa oleifera seeds","volume":"114","author":"Ullah","year":"2015","journal-title":"468(1-2)"},{"key":"B109","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.ijbiomac.2018.03.164","article-title":"Thrombin-like Enzymes from Snake Venom: Structural Characterization and Mechanism of Action","volume":"114","author":"Ullah","year":"2018","journal-title":"Int. J. Biol. Macromolecules"},{"key":"B97","doi-asserted-by":"publisher","first-page":"640819","DOI":"10.3389\/fmolb.2021.640819","article-title":"Inhibition of SARS-CoV-2 3CL Mpro by Natural and Synthetic Inhibitors: Potential Implication for Vaccine Production against COVID-19","volume":"8","author":"Ullah","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jmb.2015.09.014","article-title":"The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes","volume":"428","author":"van Zundert","year":"2016","journal-title":"J. Mol. Biol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"10239","DOI":"10.1021\/bi990721e","article-title":"The Crystal Structure of Exfoliative Toxin B: A Superantigen with Enzymatic Activity,","volume":"38","author":"Vath","year":"1999","journal-title":"Biochemistry"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1021\/bi962614f","article-title":"The Structure of the Superantigen Exfoliative Toxin A Suggests a Novel Regulation as a Serine Protease,","volume":"36","author":"Vath","year":"1997","journal-title":"Biochemistry"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and Testing of a General AMBER Force Field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B102","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology Modelling of Protein Structures and Complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B103","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/cpbi.3","article-title":"Comparative Protein Structure Modeling Using MODELLER","volume":"54","author":"Webb","year":"2016","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"B104","doi-asserted-by":"publisher","first-page":"5835","DOI":"10.1128\/iai.70.10.5835-5845.2002","article-title":"Identification of the Staphylococcus aureus Etd Pathogenicity Island Which Encodes a Novel Exfoliative Toxin, ETD, and EDIN-B","volume":"70","author":"Yamaguchi","year":"2002","journal-title":"Infect. Immun."},{"key":"B105","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/j.1469-0691.2006.01410.x","article-title":"Distribution of the Exfoliative Toxin D Gene in Clinical Staphylococcus aureus Isolates in France","volume":"12","author":"Yamasaki","year":"2006","journal-title":"Clin. Microbiol. Infect."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.800970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T10:09:31Z","timestamp":1645178971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.800970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":109,"alternative-id":["10.3389\/fphar.2022.800970"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.800970","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"800970"}}