6VOT
Crystal structure of Pseudomonas aerugonisa PBP3 complexed to gamma-lactam YU253434
Summary for 6VOT
| Entry DOI | 10.2210/pdb6vot/pdb |
| Descriptor | Peptidoglycan D,D-transpeptidase FtsI, 1-[(2S)-2-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}-3-oxopropyl]-4-{[2-(5,6 -dihydroxy-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]carbamoyl}-2,5-dihydro-1H-pyrazole-3-carboxylic acid (3 entities in total) |
| Functional Keywords | inhibitor complex, penicillin-binding protein, antibiotic, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 1 |
| Total formula weight | 59018.08 |
| Authors | van den Akker, F. (deposition date: 2020-01-31, release date: 2020-05-13, Last modification date: 2024-10-23) |
| Primary citation | Goldberg, J.A.,Nguyen, H.,Kumar, V.,Spencer, E.J.,Hoyer, D.,Marshall, E.K.,Cmolik, A.,O'Shea, M.,Marshall, S.H.,Hujer, A.M.,Hujer, K.M.,Rudin, S.D.,Domitrovic, T.N.,Bethel, C.R.,Papp-Wallace, K.M.,Logan, L.K.,Perez, F.,Jacobs, M.R.,van Duin, D.,Kreiswirth, B.M.,Bonomo, R.A.,Plummer, M.S.,van den Akker, F. A gamma-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli. J.Med.Chem., 63:5990-6002, 2020 Cited by PubMed Abstract: Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, , are reported along with the finding that is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of binding to its target PBP3. PubMed: 32420736DOI: 10.1021/acs.jmedchem.0c00255 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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