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Title
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Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation.
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Authors
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J.A.Bertrand,
D.Pignol,
J.P.Bernard,
J.M.Verdier,
J.C.Dagorn,
J.C.Fontecilla-Camps.
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Ref.
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Embo J, 1996,
15,
2678-2684.
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PubMed id
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Abstract
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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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