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首页> 外文期刊>Journal of Nuclear Physics, Material Sciences, Radiation and Applications >In silico Analysis of the Structural Properties of PSMA and its Energetic Relationship with Zn as Cofactor
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In silico Analysis of the Structural Properties of PSMA and its Energetic Relationship with Zn as Cofactor

机译：PSMA结构特性的计算机分析及其与锌作为辅因子的能量关系

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摘要

The prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with enzymatic activity similar to the family of zinc-dependent exopeptidases. This protein is of great medical and pharmacological interest as overexpression in prostate cells is related to the progression of prostate cancer; therefore, it represents an important target for the design of radiopharmaceuticals. The presence of two Zn2+ ions in the active site is crucial to the enzymatic activity and the design of high-affinity inhibitors. The amino acid residues coordinating these ions are highly conserved in PSMA orthologs from plants to mammals, and site-mutagenesis assays of these residues show a loss of enzymatic function or reduction of the kinetic parameters. In the present work, we performed molecular dynamics simulation of PSMA with the purpose of characterizing it energetically and structurally. We elucidated the differences of PSMA with its two Zn+2 ions as cofactors and without them in the free energy profile, and in four structural parameters: root mean square deviations and root mean square fluctuations by atom and amino acid residue, radius of gyration, and solvent accessible surface area.
机译：前列腺特异性膜抗原（PSMA）是一种100 kDa的II型跨膜糖蛋白，具有类似于锌依赖性外肽酶家族的酶活性。由于前列腺细胞中的过度表达与前列腺癌的进展有关，因此这种蛋白质具有重要的医学和药理学意义。因此，它代表了放射性药物设计的重要目标。活性位点中两个Zn2 +离子的存在对于酶活性和高亲和力抑制剂的设计至关重要。从植物到哺乳动物的PSMA直系同源物中，与这些离子配位的氨基酸残基高度保守，这些残基的位点诱变分析显示酶功能丧失或动力学参数降低。在目前的工作中，我们进行了PSMA的分子动力学模拟，目的是对其进行能量和结构上的表征。我们阐明了PSMA及其两个Zn + 2离子作为辅因子的情况，以及在没有自由能谱的情况下，在四个结构参数中的差异：均方根偏差和因原子和氨基酸残基引起的均方根波动，回转半径，和溶剂可及的表面积。

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