title: Metal Ion Capture Mechanism of a Copper Metallochaperone.
abstract: A novel cation-π interaction between the bound Cu(+) metal ion and Trp44 in the periplasmic Cu(+)/Ag(+) metallochaperone Escherichia coli CusF protects Cu(+) from the oxidative influence of the periplasm. In a popular model of metal ion transfer, a conformational change in the metal binding loop disrupts the cation-π interaction and moves Trp44 aside to provide access to the occluded metal ion binding site in an "open" conformation. In this study, our molecular dynamics simulations support this putative mechanism of metal ion transfer. We find that the apoprotein undergoes a transition back and forth from the crystallographically observed "closed" state to the hypothesized open conformation over multiple microseconds. In agreement with nuclear magnetic resonance data, our simulations show that similar transitions are prohibited in Cu(+)·CusF, suggesting that the conformational transitions are gated by a metal ion-mediated second-shell hydrogen bond between metal binding residue His36 and Asp37 of the metal binding loop region. Ab initio quantum mechanical calculations indicate that metal ion binding strengthens this interaction significantly, much like what is found in the case of other metalloproteins. The study builds toward a common evolutionary role of metal ion-mediated second-shell hydrogen bonds in metalloprotein structure and function.
authors.affiliation: Institute for Cyber Enabled Research, Michigan State University , 567 Wilson Road, East Lansing, Michigan 48824, United States.|Department of Chemistry, University of New Orleans , 2000 Lakeshore Drive, New Orleans, Louisiana 70148, United States.|Department of Chemistry and Quantum Theory Project, University of Florida , Gainesville, Florida 32611-8435, United States.|Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Dhruva K
authors.initials: DK
authors.lastname: Chakravorty
authors.affiliation: Department of Chemistry and Quantum Theory Project, University of Florida , Gainesville, Florida 32611-8435, United States.|Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of New Orleans , 2000 Lakeshore Drive, New Orleans, Louisiana 70148, United States.
authors.forename: Trang T
authors.initials: TT
authors.lastname: Tran
authors.affiliation: Department of Chemistry & Biochemistry, Old Dominion University , Norfolk, Virginia 23529, United States.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bayse
authors.affiliation: Institute for Cyber Enabled Research, Michigan State University , 567 Wilson Road, East Lansing, Michigan 48824, United States.|Department of Chemistry and Quantum Theory Project, University of Florida , Gainesville, Florida 32611-8435, United States.|Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Merz
mesh_terms: D001059:Apoproteins / Q000737:chemistry; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics; D003300:Copper / Q000737:chemistry*; D000079922:Copper Transport Proteins; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D001059:Apoproteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; C506213:CusF protein, E coli; D029968:Escherichia coli Proteins; D003300:Copper