S100A1: Structure, Function, and Therapeutic Potential.
S100A1: Structure, Function, and Therapeutic Potential.
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DOI：
10.2174/187231309788166460
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发表时间：
2009-05-01
影响因子：
--
通讯作者：
Weber DJ
中科院分区：
文献类型：
--
作者：
Wright NT;Cannon BR;Zimmer DB;Weber DJ
S100A1是钙结合蛋白S100家族中的一员。与大多数S100蛋白一样，S100A1在与许多蛋白质靶标相互作用所必需的钙结合后，经历了巨大的构象变化。S100A1的靶标包括与钙信号传导有关的蛋白质(兰尼定受体1和2、SERCA2a、phopholamban)、神经递质释放(突触素I和II)、细胞骨架和细丝相关蛋白(Capz、微管、中间丝、tau、微丝、结蛋白、微管蛋白、F-肌动蛋白、肌蛋白和胶质纤维酸性蛋白GFAP)、转录因子及其调节因子(例如myoD、p53)、酶(例如缩醛酶、磷酸葡萄糖变位酶、苹果酸脱氢酶、糖原磷酸化酶、光鸟苷受体环化酶、腺苷环化酶、甘油醛-3-磷酸脱氢酶、twittin、NDR、F1和ATP合成酶)、转录因子及其调节因子(例如：myoD、p53)、酶(例如：缩醛酶、磷酸葡萄糖变位酶、苹果酸脱氢酶、糖原磷酸化酶、光鸟苷环化酶、腺苷环化酶、甘油醛-3-磷酸脱氢酶、twitin、NDR、F1和ATP合成酶)。以及其他钙激活蛋白(Annexins V&VI、S100B、S100A4、S100P和其他S100蛋白)。人们对开发S100A1的抑制剂也越来越感兴趣，因为它们可能有助于治疗各种人类疾病，包括神经系统疾病、糖尿病、心力衰竭和几种类型的癌症。S100A1基因敲除小鼠中没有明显的表型，这提供了一些早期迹象，表明S100A1拮抗剂在正常组织中可能具有最小的副作用。然而，S100A1介导的治疗方法的开发因S100A1的S既作为细胞内信号分子又作为分泌蛋白的不同寻常的能力而变得复杂。此外，许多S100A1蛋白靶标最近才被确定，因此充分表征这些S100A1靶标复合体及其所产生的功能是必要的先决条件。
S100A1 is a member of the S100 family of calcium-binding proteins. As with most S100 proteins, S100A1 undergoes a large conformational change upon binding calcium as necessary to interact with numerous protein targets. Targets of S100A1 include proteins involved in calcium signaling (ryanidine receptors 1 & 2, Serca2a, phopholamban), neurotransmitter release (synapsins I & II), cytoskeletal and filament associated proteins (CapZ, microtubules, intermediate filaments, tau, mocrofilaments, desmin, tubulin, F-actin, titin, and the glial fibrillary acidic protein GFAP), transcription factors and their regulators (e.g. myoD, p53), enzymes (e.g. aldolase, phosphoglucomutase, malate dehydrogenase, glycogen phosphorylase, photoreceptor guanyl cyclases, adenylate cyclases, glyceraldehydes-3-phosphate dehydrogenase, twitchin kinase, Ndr kinase, and F1 ATP synthase), and other Ca2+-activated proteins (annexins V & VI, S100B, S100A4, S100P, and other S100 proteins). There is also a growing interest in developing inhibitors of S100A1 since they may be beneficial for treating a variety of human diseases including neurological diseases, diabetes mellitus, heart failure, and several types of cancer. The absence of significant phenotypes in S100A1 knockout mice provides some early indication that an S100A1 antagonist could have minimal side effects in normal tissues. However, development of S100A1-mediated therapies is complicated by S100A1’s unusual ability to function as both an intracellular signaling molecule and as a secreted protein. Additionally, many S100A1 protein targets have only recently been identified, and so fully characterizing both these S100A1-target complexes and their resulting functions is a necessary prerequisite.