| Autor: |
Avinash S. Punekar, Firdaus Samsudin, Adrian J. Lloyd, Christopher G. Dowson, David J. Scott, Syma Khalid, David I. Roper |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
The Cell Surface, Vol 2, Iss , Pp 54-66 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2468-2330 |
| DOI: |
10.1016/j.tcsw.2018.06.002 |
| Popis: |
Bacterial peptidoglycan glycosyltransferases (PGT) catalyse the essential polymerization of lipid II into linear glycan chains required for peptidoglycan biosynthesis. The PGT domain is composed of a large head subdomain and a smaller jaw subdomain and can be potently inhibited by the antibiotic moenomycin A (MoeA). We present an X-ray structure of the MoeA-bound Staphylococcus aureus monofunctional PGT enzyme, revealing electron density for a second MoeA bound to the jaw subdomain as well as the PGT donor site. Isothermal titration calorimetry confirms two drug-binding sites with markedly different affinities and positive cooperativity. Hydrophobic cluster analysis suggests that the membrane-interacting surface of the jaw subdomain has structural and physicochemical properties similar to amphipathic cationic α-helical antimicrobial peptides for lipid II recognition and binding. Furthermore, molecular dynamics simulations of the drug-free and -bound forms of the enzyme demonstrate the importance of the jaw subdomain movement for lipid II selection and polymerization process and provide molecular-level insights into the mechanism of peptidoglycan biosynthesis by PGTs. Keywords: Bacterial cell wall, Lipid II, Peptidoglycan synthesis, Glycosyltransferases, Jaw subdomain, Antibiotic resistance, Moenomycin A, Antimicrobial peptide |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect