Function, structure, and mechanism of intracellular copper trafficking proteins.

Abstract:

:Genetic, biochemical, and spectroscopic studies have established a new function for an intracellular protein, i.e., guiding and inserting a copper cofactor into the active site of a target enzyme. Studies of these new proteins have revealed a fundamental aspect of copper physiology, namely the vast overcapacity of the cytoplasm for copper sequestration. This finding framed the mechanistic, energetic, and structural aspects of intracellular copper trafficking proteins. One hallmark of the copper chaperones is the similarity of the protein fold between the chaperone and its target enzyme. The surface residues presented by each partner, however, are quite different, and some initial findings concerning the complementarity of these interfaces have led to mechanistic insights. The copper chaperones appear to lower the activation barrier for metal transfer into specific protein-binding sites. The manner in which they facilitate metal insertion appears to involve a docking of the metal donor and acceptor sites in close proximity to one another. Although the intimate mechanism is still open, it appears that a low activation barrier for metal transfer is achieved by a network of coordinate-covalent, electrostatic, and hydrogen bonding interactions in the vicinity of the metal-binding site itself.

journal_name

Annu Rev Biochem

authors

Huffman DL,O'Halloran TV

doi

10.1146/annurev.biochem.70.1.677

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

677-701

eissn

0066-4154

issn

1545-4509

pii

70/1/677

journal_volume

70

pub_type

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