Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation.
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.
Bertrand
J A
JA
Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale J.P. Ebel, CEA-CNRS, France.
Pignol
D
D
Bernard
J P
JP
Verdier
J M
JM
Dagorn
J C
JC
Fontecilla-Camps
J C
JC
D000595:Amino Acid Sequence; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000648:ultrastructure*; D018360:Crystallography, X-Ray; D006801:Humans; D051847:Lithostathine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010179:Pancreas / Q000737:chemistry; D017434:Protein Structure, Tertiary
D002135:Calcium-Binding Proteins; D051847:Lithostathine; D009419:Nerve Tissue Proteins; C497617:REG1A protein, human