Mechanism of Calcite Crystal Growth Inhibition by the N-terminal Undecapeptide of Lithostathine

@article{citeulike:2397044, abstract = {Pancreatic juice is supersaturated with calcium carbonate. Calcite crystals therefore may occur, obstruct pancreatic ducts, and finally cause a lithiasis. Human lithostathine, a protein synthesized by the pancreas, inhibits the growth of calcite crystals by inducing a habit modification: the rhombohedral {10 [1]4} usual habit is transformed into a needle-like habit through the {11 [IMG]img001.gif" ALT="">0} crystal form. A similar observation was made with the N-terminal undecapeptide (pE1R11) of lithostathine. We therefore aimed at discovering how peptides inhibit calcium salt crystal growth. We solved the complete x-ray structure of lithostathine, including the flexible N-terminal domain, at 1.3 A. Docking studies of pE1R11 with the (10 [1]4) and (11 [IMG]img001.gif" ALT="">0) faces through molecular dynamics simulation resulted in three successive steps. First, the undecapeptide progressively unfolded as it approached the calcite surface. Second, mobile lateral chains of amino acids made hydrogen bonds with the calcite surface. Last, electrostatic bonds between calcium ions and peptide bonds stabilized and anchored pE1R11 on the crystal surface. pE1R11-calcite interaction was stronger with the (11 [IMG]img001.gif" ALT="">0) face than with the (10 [1]4) face, confirming earlier experimental observations. Energy contributions showed that the peptide backbone governed the binding more than did the lateral chains. The ability of peptides to inhibit crystal growth is therefore essentially based on backbone flexibility. 10.1074/jbc.275.2.1057}, author = {Gerbaud, Vincent and Pignol, David and Loret, Erwann and Bertrand, Jay A. and Berland, Yvon and Fontecilla-Camps, Juan-Carlos and Canselier, Jean-Paul and Gabas, Nadine and Verdier, Jean-Michel }, citeulike-article-id = {2397044}, doi = {10.1074/jbc.275.2.1057}, journal = {J. Biol. Chem.}, month = {January}, number = {2}, pages = {1057--1064}, posted-at = {2008-06-25 13:12:36}, priority = {2}, title = {Mechanism of Calcite Crystal Growth Inhibition by the N-terminal Undecapeptide of Lithostathine}, url = {http://dx.doi.org/10.1074/jbc.275.2.1057}, volume = {275}, year = {2000} }

TY - JOUR ID - citeulike:2397044 L3 - citeulike-article-id:2397044 TI - Mechanism of Calcite Crystal Growth Inhibition by the N-terminal Undecapeptide of Lithostathine JF - J. Biol. Chem. VL - 275 IS - 2 SP - 1057 EP - 1064 N2 - Pancreatic juice is supersaturated with calcium carbonate. Calcite crystals therefore may occur, obstruct pancreatic ducts, and finally cause a lithiasis. Human lithostathine, a protein synthesized by the pancreas, inhibits the growth of calcite crystals by inducing a habit modification: the rhombohedral {10 [1]4} usual habit is transformed into a needle-like habit through the {11 [IMG]img001.gif" ALT="">0} crystal form. A similar observation was made with the N-terminal undecapeptide (pE1R11) of lithostathine. We therefore aimed at discovering how peptides inhibit calcium salt crystal growth. We solved the complete x-ray structure of lithostathine, including the flexible N-terminal domain, at 1.3 A. Docking studies of pE1R11 with the (10 [1]4) and (11 [IMG]img001.gif" ALT="">0) faces through molecular dynamics simulation resulted in three successive steps. First, the undecapeptide progressively unfolded as it approached the calcite surface. Second, mobile lateral chains of amino acids made hydrogen bonds with the calcite surface. Last, electrostatic bonds between calcium ions and peptide bonds stabilized and anchored pE1R11 on the crystal surface. pE1R11-calcite interaction was stronger with the (11 [IMG]img001.gif" ALT="">0) face than with the (10 [1]4) face, confirming earlier experimental observations. Energy contributions showed that the peptide backbone governed the binding more than did the lateral chains. The ability of peptides to inhibit crystal growth is therefore essentially based on backbone flexibility. 10.1074/jbc.275.2.1057 AU - Gerbaud, Vincent AU - Pignol, David AU - Loret, Erwann AU - Bertrand, Jay AU - Berland, Yvon AU - Fontecilla-Camps, Juan-Carlos AU - Canselier, Jean-Paul AU - Gabas, Nadine AU - Verdier, Jean-Michel PY - 2000/01/14/ UR - http://dx.doi.org/10.1074/jbc.275.2.1057 ER -