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Dioxygenation of Human Serum Albumin Having a Prosthetic Heme Group in a Tailor-Made Heme Pocket
Ist Teil von
Journal of the American Chemical Society, 2004-11, Vol.126 (44), p.14304-14305
Ort / Verlag
Washington, DC: American Chemical Society
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Human serum albumin (HSA) is the most abundant plasma protein in our bloodstream and serves as a transporter for small hydrophobic molecules such as fatty acids, bilirubin, and steroids. Hemin dissociated from methemoglobin is also bound within a narrow D-shaped cavity in subdomain IB of HSA. In terms of the general hydrophobicity of the α-helical pocket, HSA potentially has features similar to the heme-binding site of myoglobin (Mb) or hemoglobin (Hb). However, the reduced ferrous HSA−heme complex is immediately oxidized by O2, because HSA lacks the proximal histidine that enables the heme group to bind O2. In this paper, we report the introduction of a proximal histidine into the subdomain IB of HSA by site-directed mutagenesis to construct a tailor-made heme pocket (I142H/Y161L), which allows a reversible O2 binding to the prosthetic heme group. Laser flash photolysis experiments revealed that this artificial hemoprotein appears to have two different geometries of the axial-imidazole coordination, and these two species (I and II) showed rather low O2 binding affinities (P 1/2 O 2 = 18 and 134 Torr) relative to those of Mb and Hb.