Molecular modulation of calcium oxalate crystallization by osteopontin and citrate
| Autor: | Salvador Zepeda, S. R. Qiu, George H. Nancollas, Andrzej Wierzbicki, Christine A. Orme, A. M. Cody, John R. Hoyer, J. J. De Yoreo |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Molecular model Sialoglycoproteins Calcium oxalate Microscopy Atomic Force law.invention Kidney Calculi chemistry.chemical_compound law medicine Citrates Osteopontin Crystallization Multidisciplinary Calcium Oxalate biology Chemistry medicine.disease Small molecule Kinetics Biochemistry Physical Sciences biology.protein Kidney stones Molecular imaging Biomineralization |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:1811-1815 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0307900100 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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