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Visualizing Biological Copper Storage: The Importance of Thiolate‐Coordinated Tetranuclear Clusters
Author(s) -
Baslé Arnaud,
Platsaki Semeli,
Dennison Christopher
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201703107
Subject(s) - copper , chemistry , cytosol , cluster (spacecraft) , metal , crystallography , ion , biochemistry , enzyme , organic chemistry , computer science , programming language
Abstract Bacteria possess cytosolic proteins (Csp3s) capable of binding large quantities of copper and preventing toxicity. Crystal structures of a Csp3 plus increasing amounts of Cu I provide atomic‐level information about how a storage protein loads with metal ions. Many more sites are occupied than Cu I equiv added, with binding by twelve central sites dominating. These can form [Cu 4 (S‐Cys) 4 ] intermediates leading to [Cu 4 (S‐Cys) 5 ] − , [Cu 4 (S‐Cys) 6 ] 2− , and [Cu 4 (S‐Cys) 5 (O‐Asn)] − clusters. Construction of the five Cu I sites at the opening of the bundle lags behind the main core, and the two least accessible sites at the opposite end of the bundle are occupied last. Facile Cu I cluster formation, reminiscent of that for inorganic complexes with organothiolate ligands, is largely avoided in biology but is used by proteins that store copper in the cytosol of prokaryotes and eukaryotes, where this reactivity is also key to toxicity.