Abstract
Methionine-rich motifs have an important role in copper trafficking factors, including the CusF protein. Here we show that CusF uses a new metal recognition site wherein Cu(I) is tetragonally displaced from a Met2His ligand plane toward a conserved tryptophan. Spectroscopic studies demonstrate that both thioether ligation and strong cation-π interactions with tryptophan stabilize metal binding. This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry.
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Acknowledgements
Research was supported by US National Institutes of Health (NIH) grants GM 38784 (to T.V.O.), GM 38047 (to J.E.P.-H.) and GM 25158 (to T.G.S.) and by National Research Service Award Postdoctoral Training Grant GM 071129 (to A.V.D.). Support from the R.H. Lurie Comprehensive Cancer Center (P30 CA060553) of Northwestern University to the Structural Biology Facility and Keck Biophysics Facility is acknowledged. Portions of this work were performed at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT, beamline 17-ID-B) at the Advanced Photon Source (APS) and at the Stanford Synchrotron Radiation Laboratory (SSRL). Use of the APS is supported by the US Department of Energy (DOE). SSRL is operated by the DOE, Office of Basic Energy Sciences. The SSRL Biotechnology Program is supported by the NIH and the DOE.
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Xue, Y., Davis, A., Balakrishnan, G. et al. Cu(I) recognition via cation-π and methionine interactions in CusF. Nat Chem Biol 4, 107–109 (2008). https://doi.org/10.1038/nchembio.2007.57
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DOI: https://doi.org/10.1038/nchembio.2007.57
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