title: Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen.
abstract: STEAP1, six-transmembrane epithelial antigen of prostate member 1, is strongly expressed in several types of cancer cells, particularly in prostate cancer, and inhibition of its expression reduces the rate of tumor cell proliferation. However, the physiological function of STEAP1 remains unknown. Here for the first time, we purified a mammalian (rabbit) STEAP1 at a milligram level, permitting its high-quality biochemical and biophysical characterizations. We found that STEAP1 likely assembles as a homotrimer and forms a heterotrimer when co-expressed with STEAP2. Each STEAP1 protomer binds one heme prosthetic group that is mainly low-spin with a pair of histidine axial ligands, with small portions of high-spin and P450-type heme. In its ferrous state, STEAP1 is capable of reducing transition metal ion complexes of Fe3+and Cu2+. Ferrous STEAP1 also reacts readily with O2through an outer sphere redox mechanism. Kinetics with all three substrates are biphasic with ∼80 and ∼20% for the fast and slow phases, respectively, in line with its heme heterogeneity. STEAP1 retained a low level of bound FAD during purification, and the binding equilibrium constant, KD, was ∼30 μM. These results highlight STEAP as a novel metal reductase and superoxide synthase and establish a solid basis for further research into understanding how STEAP1 activities may affect cancer progression.
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States.
authors: Kwangsoo
authors: K
authors: Kim
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States.
authors: Sharmistha
authors: S
authors: Mitra
authors: Division of Hematology, Department of Internal Medicine, University of Texas-McGovern Medical School , Houston, Texas 77030, United States.
authors: Gang
authors: G
authors: Wu
authors: Division of Hematology, Department of Internal Medicine, University of Texas-McGovern Medical School , Houston, Texas 77030, United States.
authors: Vladimir
authors: V
authors: Berka
authors: Skirball Institute of Biomolecular Medicine, New York University School of Medicine , New York, New York 10016, United States.
authors: Jinmei
authors: J
authors: Song
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States.|Institute of Medical Sciences and Department of Pharmacology, Shanghai Jiao Tong University School of Medicine , Shanghai 200025, China.
authors: Ye
authors: Y
authors: Yu
authors: Department of Chemistry, College of Staten Island , Staten Island, New York 10314, United States.
authors: Sebastien
authors: S
authors: Poget
authors: Skirball Institute of Biomolecular Medicine, New York University School of Medicine , New York, New York 10016, United States.
authors: Da-Neng
authors: DN
authors: Wang
authors: Division of Hematology, Department of Internal Medicine, University of Texas-McGovern Medical School , Houston, Texas 77030, United States.
authors: Ah-Lim
authors: AL
authors: Tsai
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, Texas 77030, United States.
authors: Ming
authors: M
authors: Zhou
mesh_terms: D000465:Algorithms; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001669:Biochemical Phenomena; D055592:Biophysical Phenomena; D002460:Cell Line; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D011817:Rabbits
chemical_list: D000951:Antigens, Neoplasm; D056831:Coordination Complexes; D008670:Metals; D006418:Heme; D003300:Copper; D007501:Iron; D010088:Oxidoreductases; C432763:STEAP1 protein, human; D010100:Oxygen