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. 1996 Jun 3;15(11):2678–2684.

Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation.

J A Bertrand 1, D Pignol 1, J P Bernard 1, J M Verdier 1, J C Dagorn 1, J C Fontecilla-Camps 1
PMCID: PMC450203  PMID: 8654365

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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Selected References

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