Abstract
Extended X-ray absorption fine structure studies of the metallo-β-lactamase L1 from Stenotrophomonas maltophilia containing 1 and 2 equiv of Zn(II) and containing 2 equiv of Zn(II) plus hydrolyzed nitrocefin are presented. The data indicate that the first, catalytically dominant metal ion is bound by L1 at the consensus Zn1 site. The data further suggest that binding of the first metal helps preorganize the ligands for binding of the second metal ion. The di-Zn enzyme displays a well-defined metal–metal interaction at 3.42 Å. Reaction with the β-lactam antibiotic nitrocefin results in a product-bound species, in which the ring-opened lactam rotates in the active site to present the S1 sulfur atom of nitrocefin to one of the metal ions for coordination. The product bridges the two metal ions, with a concomitant lengthening of the Zn–Zn interaction to 3.62 Å.
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Acknowledgements
Financial support for this work was provided by the National Institutes of Health (P20RR-16480 from the BRIN/INBRE Program of the National Center for Research Resources to D.L.T. and GM40052 to M.W.C.). The National Synchrotron Light Source is supported by the US Department of Energy.
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Costello, A., Periyannan, G., Yang, KW. et al. Site-selective binding of Zn(II) to metallo-β-lactamase L1 from Stenotrophomonas maltophilia . J Biol Inorg Chem 11, 351–358 (2006). https://doi.org/10.1007/s00775-006-0083-z
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DOI: https://doi.org/10.1007/s00775-006-0083-z