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      Molecular modulation of calcium oxalate crystallization by osteopontin and citrate

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          Abstract

          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.

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          Most cited references16

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          Interactions between acidic proteins and crystals: stereochemical requirements in biomineralization.

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            Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin.

            Bone sialoprotein (BSP) and osteopontin (OPN) are two members of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of genetically related proteins that are clustered on human chromosome 4. We present evidence that this entire family is the result of duplication and subsequent divergent evolution of a single ancient gene. The solution structures of these two post-translationally modified recombinant proteins were solved by one dimensional proton NMR and transverse relaxation times. The polypeptide backbones of both free BSP and OPN rapidly sample an ensemble of conformations consistent with them both being completely unstructured in solution. This flexibility appears to enable these relatively small glycoproteins to rapidly associate with a number of different binding partners including other proteins as well as the mineral phase of bones and teeth. These proteins often function by bridging two proteins of fixed structures into a biologically active complex. Copyright 2001 Academic Press.
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              Thermodynamics of Calcite Growth: Baseline for Understanding Biomineral Formation

              H H Teng (1998)
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                PNAS
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                February 17 2004
                February 17 2004
                February 17 2004
                February 06 2004
                : 101
                : 7
                : 1811-1815
                Article
                10.1073/pnas.0307900100
                357009
                14766970
                75aa942b-c4b6-4192-9f8e-a31a94111e0e
                © 2004
                History

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