biostudies-literatureXue YNCI NIH HHSNIGMS NIH HHS107-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC2850561biostudies-literatureUnknown4(2)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-pi interactions with tryptophan stabilize metal binding. This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry.Nature chemical biologyCu(I) recognition via cation-pi and methionine interactions in CusF.PMC2850561GM 25158R37 GM038784-21GM 38784GM 38047R01 GM038784R01 GM038047P30 CA060553GM 071129F32 GM071129R37 GM038784R01 GM025158Focia PStaehlin BMPenner-Hahn JEDavis AVStasser JPO'Halloran TVBalakrishnan GSpiro TGXue YfalseCu(I) recognition via cation-pi and methionine interactions in CusF.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-pi interactions with tryptophan stabilize metal binding. This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry.2008-01-01T00:00:00Z2008 Feb2024-11-07T14:00:54.401Z2019-03-27T00:29:55ZS-EPMC28505611815712410.1038/nchembio.2007.57