Evgenii S. Kuchaev, Sergey V. Efimov, Alexander V. Klochkov, Albert V. Aganov, Polina M. Ivantcova, Konstantin V. Kudryavtsev, Konstantin S. Usachev
{"title":"Solution NMR Studies of LPRDA Peptide: an Oligopeptide Inhibitor of Staphylococcus aureus Sortase A","authors":"Evgenii S. Kuchaev, Sergey V. Efimov, Alexander V. Klochkov, Albert V. Aganov, Polina M. Ivantcova, Konstantin V. Kudryavtsev, Konstantin S. Usachev","doi":"10.1007/s00723-023-01635-7","DOIUrl":null,"url":null,"abstract":"<div><p>Sortases are Gram-positive bacterial extracellular transpeptidases involved in the attachment of surface proteins to the cell wall. The mechanism of action of Staphylococcus aureus Sortase A (SrtA) is based on specific recognition of the LPXTG motive at the C-terminus of the surface protein, cleavage of this site between threonine and glycine residues, subsequent transfer of the N-terminal transmembrane domain to the amino group of the pentaglycine linker and thus anchoring of proteins with this motive on the cell surface. As SrtA is involved in both early and late stages of bacterial infection because it attaches adhesins and immune evasion proteins to the cell wall, this enzyme is a good target for combating bacterial infections. The oligopeptide LPRDA was recently found to be an effective inhibitor of the enzymatic activity of SrtA through competitive binding to its active site. By NMR spectroscopy we solved the solution structure of the LPRDA peptide and showed the presence of several conformers in solution. The obtained data are the basis for further studies of the structure and function of peptidomimetics based on LPRDA oligopeptide.</p></div>","PeriodicalId":469,"journal":{"name":"Applied Magnetic Resonance","volume":"55 4","pages":"451 - 461"},"PeriodicalIF":1.1000,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Applied Magnetic Resonance","FirstCategoryId":"101","ListUrlMain":"https://link.springer.com/article/10.1007/s00723-023-01635-7","RegionNum":4,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHYSICS, ATOMIC, MOLECULAR & CHEMICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Sortases are Gram-positive bacterial extracellular transpeptidases involved in the attachment of surface proteins to the cell wall. The mechanism of action of Staphylococcus aureus Sortase A (SrtA) is based on specific recognition of the LPXTG motive at the C-terminus of the surface protein, cleavage of this site between threonine and glycine residues, subsequent transfer of the N-terminal transmembrane domain to the amino group of the pentaglycine linker and thus anchoring of proteins with this motive on the cell surface. As SrtA is involved in both early and late stages of bacterial infection because it attaches adhesins and immune evasion proteins to the cell wall, this enzyme is a good target for combating bacterial infections. The oligopeptide LPRDA was recently found to be an effective inhibitor of the enzymatic activity of SrtA through competitive binding to its active site. By NMR spectroscopy we solved the solution structure of the LPRDA peptide and showed the presence of several conformers in solution. The obtained data are the basis for further studies of the structure and function of peptidomimetics based on LPRDA oligopeptide.
期刊介绍:
Applied Magnetic Resonance provides an international forum for the application of magnetic resonance in physics, chemistry, biology, medicine, geochemistry, ecology, engineering, and related fields.
The contents include articles with a strong emphasis on new applications, and on new experimental methods. Additional features include book reviews and Letters to the Editor.