The X-ray structure of the adduct formed upon reaction of aurothiomalate with apo-transferrin: gold binding sites and a unique transferrin structure along the apo/holo transition pathway

Abstract

The interaction of sodium aurothiomalate with the apo-form of human serum transferrin (hTF) was studied by X-ray crystallography. The protein binds gold ions close to the side chains of His25, Asp63 and His249, His207 and Tyr238, His273, His289, His300, His473, His585, His598, His606, and His642; the thiomalate ligand is released. Notably, the N- and C-lobes of one of the two hTF molecules in the asymmetric unit of the Au-hTF adduct crystals exhibit conformations that are slightly different from those observed in the “fully-opened” apo-hTF, with the N-lobe that is intermediate between the “partially-opened” form observed in the structure of hTF with Bi3+ and the “fully-opened” form of apo-hTF. Thus, our data provide relevant information on the binding of gold centers to hTF and on a unique hTF structure along the apo-hTF/holo-hTF transition pathway.