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Publication Abstract from PubMed

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-beta-lactamase (MbetaL) that confers resistance to beta-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 A apart and the iron is high-spin Fe3+ , which produces only small PCSs. [FeZn]-MbetaLs may be important drug targets, as [FeZn]-IMP-1 is enzymatically active and readily produced in the presence of small amounts of Fe3+ .

Iron(III) Located in the Dinuclear Metallo-beta-Lactamase IMP-1 by Pseudocontact Shifts.,Carruthers TJ, Carr PD, Loh CT, Jackson CJ, Otting G Angew Chem Int Ed Engl. 2014 Oct 15. doi: 10.1002/anie.201408693. PMID:25320022^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.