Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. |
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Authors: | J A Bertrand D Pignol J P Bernard J M Verdier J C Dagorn and J C Fontecilla-Camps |
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Affiliation: | Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale J.P. Ebel, CEA-CNRS, France. |
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Abstract: | Human lithostathine (HLIT) is a pancreatic glycoprotein which inhibits the growth and nucleation of calcium carbonate crystals. The crystal structure of the monomeric 17 kDa HLIT, determined to a resolution of 1.55 angstroms, was refined to a crystallographic R-factor of 18.6%. Structural comparison with the carbohydrate-recognition domains of rat mannose-binding protein and E-selectin indicates that the C-terminal domain of HLIT shares a common architecture with the C-type lectins. Nevertheless, HLIT does not bind carbohydrate nor does it contain the characteristic calcium-binding sites of the C-type lectins. In consequence, HLIT represents the first structurally characterized member of this superfamily which is not a lectin. Analysis of the charge distribution and calculation of its dipole moment reveal that HLIT is a strongly polarized molecule. Eight acidic residues which are separated by regular 6 angstrom spacings form a unique and continuous patch on the molecular surface. This arrangement coincides with the distribution of calcium ions on certain planes of the calcium carbonate crystal; the dipole moment of HLIT may play a role in orienting the protein on the crystal surface prior to the more specific interactions of the acidic residues. |
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