Molecular modulation of calcium oxalate crystallization by osteopontin and citrate
Molecular modulation of calcium oxalate crystallization by osteopontin and citrate
复制标题
骨蛋白酶和柠檬酸盐对草酸钙结晶的分子调节作用
DOI：
10.1073/pnas.0307900100
复制
发表时间：
2004-02-17
影响因子：
11.1
通讯作者：
De Yoreo, JJ
中科院分区：
文献类型：
--
作者：
Qiu, SR;Wierzbicki, A;De Yoreo, JJ
一水草酸钙(COM)在植物生理中起着重要作用，是人类慢性疾病的来源之一，是肾结石的主要无机成分。了解生物控制COM结晶的分子机制是开发有效的石病治疗方法的核心，并有助于定义合成生物启发材料的一般策略。到目前为止，蛋白质和小分子修饰COM的研究还没有解决分子尺度的调控机制。此外，由于指导COM抑制的蛋白质已经被鉴定和测序，它们为生物矿化的一般物理化学研究提供了基础。在这里，我们报告了两种尿液成分，骨桥蛋白和柠檬酸盐，一种常见的治疗剂，对共同调节的分子尺度的看法。我们将力显微镜和分子模拟相结合，通过特定的相互作用将台阶运动钉在不同的面上，从而控制生长习性和动力学，其中尺寸和结构共同决定了作用的有效性。此外，研究结果表明，这两种修饰剂的同时作用可能会产生相加效应，以抑制晶体的整体生长，并证明结合分子成像和建模工具对了解疾病异常结晶发生的事件的有效性。
Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is a source of chronic human disease, forming the major inorganic component of kidney stones. Understanding molecular mechanisms of biological control over COM crystallization is central to development of effective stone disease therapies and can help define general strategies for synthesizing biologically inspired materials. To date, research on COM modification by proteins and small molecules has not resolved the molecular-scale control mechanisms. Moreover, because proteins directing COM inhibition have been identified and sequenced, they provide a basis for general physiochemical investigations of biomineralization. Here, we report molecular-scale views of COM modulation by two urinary constituents, the protein osteopontin and citrate, a common therapeutic agent. Combining force microscopy with molecular modeling, we show that each controls growth habit and kinetics by pinning step motion on different faces through specific interactions in which both size and structure determine the effectiveness. Moreover, the results suggest potential for additive effects of simultaneous action by both modifiers to inhibit the overall growth of the crystal and demonstrate the utility of combining molecular imaging and modeling tools for understanding events underlying aberrant crystallization in disease.