9.B.158 The Cut Copper Homeostasis (Cut) Family 

CutC is one of the six members of Cut family proteins, involved in prokaryotic copper homeostasis. The human homolog of CutC (hCutC) is an intracellular copper-binding protein with unknown physiological function. The Cut protein family is associated with copper homeostasis and involved in uptake, storage, delivery, and efflux of copper. CutC is a member of the Cut family and is suggested to be involved in efflux trafficking of cuprous ion. Li et al. 2010 reported the biochemical and structural characterization of human CutC (hCutC). hCutC can bind Cu⁺ with a stoichiometry of 1:1 and an apparent dissociation constant of 15.5+/-2.8 microM. hCutC assumes a typical TIM-barrel fold and forms a tetramer in both crystal structure and solution which is different from the dimeric architecture of the bacterial CutC. Structure analysis and sequence comparison of CutC proteins from different species revealed two strictly conserved Cys residues on the inner surface of the C-terminal end of the TIM-barrel. Mutations of the two Cys residues impair the ability of hCutC to bind Cu⁺. Their results suggest that hCutC functions as an enzyme with Cu⁺ as a cofactor rather than a copper transporter.  The potential Cu⁺-binding site consists of the two Cys residues and other conserved residues in the vicinity.