4UAM

1.8 Angstrom crystal structure of IMP-1 metallo-beta-lactamase with a mixed iron-zinc center in the active site

Summary for 4UAM

• Entry DOI: 10.2210/pdb4uam/pdb
• Descriptor: IMP-1 metallo-beta-lactamase, FE (III) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: antibiotic resistance, binuclear metal center, hydrolase
• Biological source: Pseudomonas aeruginosa NCGM2.S1
• Total number of polymer chains: 4
• Total formula weight: 101828.12

Authors

Carruthers, T.J.,Carr, P.D.,Jackson, C.J.,Otting, G. (deposition date: 2014-08-11, release date: 2014-09-17, Last modification date: 2024-10-16)

Primary citation

Carruthers, T.J.,Carr, P.D.,Loh, C.T.,Jackson, C.J.,Otting, G.
Iron(III) Located in the Dinuclear Metallo-beta-Lactamase IMP-1 by Pseudocontact Shifts.
Angew.Chem.Int.Ed.Engl., 53:14269-14272, 2014

PubMed Abstract: Heterodinuclear metalloenzymes are an important class of metalloproteins, but determining the location of the different metal ions can be difficult. Herein we present a new NMR spectroscopy method that uses pseudocontact shifts (PCS) to achieve this without assumptions about the coordinating ligands. The approach is illustrated with the dinuclear [FeZn] complex of IMP-1, which is a prototypical metallo-β-lactamase (MβL) that confers resistance to β-lactam antibiotics. Results from single-crystal X-ray diffraction were compromised by degradation during crystallization. With [GaZn]-IMP-1 as diamagnetic reference, the PCSs unambiguously identified the iron binding site in fresh samples of [FeZn]-IMP-1, even though the two metal centers are less than 3.8 Å apart and the iron is high-spin Fe(3+), which produces only small PCSs. [FeZn]-MβLs may be important drug targets, as [FeZn]-IMP-1 is enzymatically active and readily produced in the presence of small amounts of Fe(3+).

PubMed: 25320022
DOI: 10.1002/anie.201408693

Experimental method

X-RAY DIFFRACTION (1.8 Å)