Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen

• DOI: 10.1021/acs.biochem.6b00610
• Publication Date: 2016-10-28T17:25:41Z
• Authors: Kwangsoo Kim; Sharmistha Mitra; Gang Wu; Vladimir Berka; Jinmei Song; Ye Yu; Sebastien Poget; Da-Neng Wang; Ah-Lim Tsai; Ming Zhou
• Keywords: 0301 basic medicine; 0303 health sciences; Biochemical Phenomena; Circular Dichroism; Iron; Electron Spin Resonance Spectroscopy; Heme; Biophysical Phenomena; Cell Line; 3. Good health; Oxygen; Kinetics; 03 medical and health sciences; Antigens, Neoplasm; Coordination Complexes; Metals; Animals; Humans; Protein Multimerization; Oxidoreductases; Oxidation-Reduction; Algorithms; Copper; Protein Binding

STEAP1, six-transmembrane epithelial antigen of prostate member 1, is strongly expressed in several types cancer cells, particularly cancer, and inhibition its expression reduces the rate tumor cell proliferation. However, physiological function STEAP1 remains unknown. Here for first time, we purified a mammalian (rabbit) at milligram level, permitting high-quality biochemical biophysical characterizations. We found that likely assembles as homotrimer forms heterotrimer when co-expressed with STEAP2. Each protomer binds one heme prosthetic group mainly low-spin pair histidine axial ligands, small portions high-spin P450-type heme. In ferrous state, capable reducing transition metal ion complexes Fe3+ Cu2+. Ferrous also reacts readily O2 through an outer sphere redox mechanism. Kinetics all three substrates are biphasic ∼80 ∼20% fast slow phases, respectively, line heterogeneity. retained low level bound FAD during purification, binding equilibrium constant, KD, was ∼30 μM. These results highlight STEAP novel reductase superoxide synthase establish solid basis further research into understanding how activities may affect progression.