Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen.
Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen.
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前列腺1（STEAP1）的六跨膜上皮抗原具有单个B血红素，能够减少金属离子复合物和氧气。
DOI：
10.1021/acs.biochem.6b00610
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发表时间：
2016-12-06
期刊：
影响因子：
2.9
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Kim K;Mitra S;Wu G;Berka V;Song J;Yu Y;Poget S;Wang DN;Tsai AL;Zhou M
STEAP 1，前列腺成员1的六跨膜上皮抗原，在几种类型的癌细胞中高度表达，特别是在前列腺癌中，抑制其表达可减少肿瘤细胞增殖。然而，STEAP 1的生理功能仍然未知。在这里，我们第一次纯化了毫克级的哺乳动物（兔）STEAP 1，使其能够进行高质量的生化和生物物理表征。我们发现STEAP 1可能组装成同源三聚体，并在与STEAP 2共表达时形成异源三聚体。每个STEAP 1原聚体结合一个血红素辅基，其主要是低自旋的，具有一对组氨酸轴向配体，加上小部分高自旋和P450型血红素。在亚铁状态下，STEAP 1能够还原Fe 3+和Cu 2+的过渡金属离子络合物。亚铁STEAP 1也容易通过外层氧化还原机制与O2反应。所有三种底物的动力学都是双相的，快相和慢相的动力学分别为~ 80%和~20%，与其血红素异质性一致。STEAP 1在纯化过程中保留低水平的结合FAD，结合平衡常数KD约为30μM。这些结果突出了STEAP作为一种新型金属还原酶和超氧化物合酶，并为进一步研究STEAP 1活性如何影响癌症进展奠定了坚实的基础。
STEAP1, Six Transmembrane Epithelial Antigen of Prostate member 1, is highly expressed in several types of cancer cells, particularly in prostate cancer, and inhibition of its expression reduces tumor cell proliferation. However, the physiological function of STEAP1 remains unknown. Here for the first time we purified a mammalian (rabbit) STEAP1 at milligram level, enabling 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 which is mainly low-spin with a pair of histidine axial ligands, plus small portions of high-spin and P450 type of heme. In its ferrous state, STEAP1 is capable of reducing transition metal ion complexes of Fe3+ and Cu2+. Ferrous STEAP1 also reacts readily with O2 through an outer sphere redox mechanism. Kinetics with all three substrates are biphasic with ~ 80% and ~20% for the fast and slow phases, in line with its heme heterogeneity. STEAP1 retained low level of bound FAD during purification and the binding equilibrium constant, KD, was ~ 30μM. These results highlight STEAP as a novel metal reductase and superoxide synthase, and establish a solid basis for further research into understanding of how STEAP1 activities may affect cancer progression.
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影响因子：
2.9
作者：
Kendrick, BS;Kerwin, BA;Philo, JS
通讯作者：
Philo, JS
DOI：
10.1073/pnas.96.25.14523
发表时间：
1999-12-07
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
Fujii, H;Finnegan, MG;Johnson, MK
通讯作者：
Johnson, MK
影响因子：
30.8
作者：
Ohgami, RS;Campagna, DR;Fleming, MD
通讯作者：
Fleming, MD
影响因子：
2.9
作者：
Sch端nemann, V;Trautwein, AX;Haehnel, W
通讯作者：
Haehnel, W