8CXR
Crystal structure of MraY bound to a sphaerimicin analogue
Summary for 8CXR
| Entry DOI | 10.2210/pdb8cxr/pdb |
| Descriptor | MraYAA nanobody, Phospho-N-acetylmuramoyl-pentapeptide-transferase, (1S,4R,5S,6R,7S,9S,10S,11S,13S,14R)-9-[(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]-14-(hexadecanoyloxy)-5,6,13-trihydroxy-8,16-dioxa-2,11-diazatricyclo[9.3.1.1~4,7~]hexadecane-10-carboxylic acid (3 entities in total) |
| Functional Keywords | mray, nanobody, sphaerimicin, membrane protein, membrane protein-transferase complex, membrane protein/transferase |
| Biological source | Lama glama More |
| Total number of polymer chains | 8 |
| Total formula weight | 225619.12 |
| Authors | Mashalidis, E.H.,Lee, S.Y. (deposition date: 2022-05-22, release date: 2023-03-29, Last modification date: 2024-11-13) |
| Primary citation | Nakaya, T.,Yabe, M.,Mashalidis, E.H.,Sato, T.,Yamamoto, K.,Hikiji, Y.,Katsuyama, A.,Shinohara, M.,Minato, Y.,Takahashi, S.,Horiuchi, M.,Yokota, S.I.,Lee, S.Y.,Ichikawa, S. Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY. Nat Commun, 13:7575-7575, 2022 Cited by PubMed Abstract: The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria. PubMed: 36539416DOI: 10.1038/s41467-022-35227-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.65 Å) |
Structure validation
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