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The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization
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Punekar, Avinash S., Samsudin, Firdaus, Lloyd, Adrian J., Dowson, Christopher G., Scott, David J., Khalid, Syma and Roper, David I. (2018) The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization. The Cell Surface, 2 . pp. 54-66. doi:10.1016/j.tcsw.2018.06.002 ISSN 2468-2330.
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Official URL: http://dx.doi.org/10.1016/j.tcsw.2018.06.002
Abstract
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.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RS Pharmacy and materia medica |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Peptidoglycans -- Synthesis, Lipids, Staphylococcus aureus, Drug resistance in microorganisms, Peptide antibiotics | ||||||||||||
| Journal or Publication Title: | The Cell Surface | ||||||||||||
| Publisher: | Elsevier | ||||||||||||
| ISSN: | 2468-2330 | ||||||||||||
| Official Date: | 20 June 2018 | ||||||||||||
| Dates: |
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| Volume: | 2 | ||||||||||||
| Page Range: | pp. 54-66 | ||||||||||||
| DOI: | 10.1016/j.tcsw.2018.06.002 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Date of first compliant deposit: | 22 June 2018 | ||||||||||||
| Date of first compliant Open Access: | 22 June 2018 | ||||||||||||
| RIOXX Funder/Project Grant: |
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