5NDE
Crystal structure of metallo-beta-lactamase SPM-1 in space group P4222
Summary for 5NDE
| Entry DOI | 10.2210/pdb5nde/pdb |
| Descriptor | Beta-lactamase IMP-1, ZINC ION, SULFATE ION, ... (6 entities in total) |
| Functional Keywords | lactamase, inhibitor, cyclobutanone, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 2 |
| Total formula weight | 57162.44 |
| Authors | Hinchliffe, P.,Spencer, J. (deposition date: 2017-03-08, release date: 2018-01-17, Last modification date: 2024-01-17) |
| Primary citation | Abboud, M.I.,Kosmopoulou, M.,Krismanich, A.P.,Johnson, J.W.,Hinchliffe, P.,Brem, J.,Claridge, T.D.W.,Spencer, J.,Schofield, C.J.,Dmitrienko, G.I. Cyclobutanone Mimics of Intermediates in Metallo-beta-Lactamase Catalysis. Chemistry, 24:5734-5737, 2018 Cited by PubMed Abstract: The most important resistance mechanism to β-lactam antibiotics involves hydrolysis by two β-lactamase categories: the nucleophilic serine and the metallo-β-lactamases (SBLs and MBLs, respectively). Cyclobutanones are hydrolytically stable β-lactam analogues with potential to inhibit both SBLs and MBLs. We describe solution and crystallographic studies on the interaction of a cyclobutanone penem analogue with the clinically important MBL SPM-1. NMR experiments using F-labeled SPM-1 imply the cyclobutanone binds to SPM-1 with micromolar affinity. A crystal structure of the SPM-1:cyclobutanone complex reveals binding of the hydrated cyclobutanone through interactions with one of the zinc ions, stabilisation of the hydrate by hydrogen bonding to zinc-bound water, and hydrophobic contacts with aromatic residues. NMR analyses using a C-labeled cyclobutanone support assignment of the bound species as the hydrated ketone. The results inform on how MBLs bind substrates and stabilize tetrahedral intermediates. They support further investigations on the use of transition-state and/or intermediate analogues as inhibitors of all β-lactamase classes. PubMed: 29250863DOI: 10.1002/chem.201705886 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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