1QDD

CRYSTAL STRUCTURE OF HUMAN LITHOSTATHINE TO 1.3 A RESOLUTION

Summary for 1QDD

• Entry DOI: 10.2210/pdb1qdd/pdb
• Related: 1LIT
• Descriptor: LITHOSTATHINE, beta-D-galactopyranose-(1-3)-[N-acetyl-alpha-neuraminic acid-(2-6)]2-acetamido-2-deoxy-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: pancreatic stone inhibitor, lithostathine, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16879.52

Authors

Gerbaud, V.,Pignol, D.,Loret, E.,Bertrand, J.A.,Berland, Y.,Fontecilla-Camps, J.C.,Canselier, J.P.,Gabas, N.,Verdier, J.M. (deposition date: 1999-05-20, release date: 1999-05-28, Last modification date: 2024-11-20)

Primary citation

Gerbaud, V.,Pignol, D.,Loret, E.,Bertrand, J.A.,Berland, Y.,Fontecilla-Camps, J.C.,Canselier, J.P.,Gabas, N.,Verdier, J.M.
Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.
J.Biol.Chem., 275:1057-1064, 2000

PubMed 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 14) usual habit is transformed into a needle-like habit through the (11 0) crystal form. A similar observation was made with the N-terminal undecapeptide (pE(1)R(11)) 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 pE(1)R(11) with the (10 14) and (11 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 pE(1)R(11) on the crystal surface. pE(1)R(11)-calcite interaction was stronger with the (11 0) face than with the (10 14) 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.

PubMed: 10625646
DOI: 10.1074/jbc.275.2.1057

Experimental method

X-RAY DIFFRACTION (1.3 Å)