PDBsum entry 1qdd

Metal binding protein

PDB id: 1qdd

Contents

Protein chain

144 a.a. *

Ligands

NDG-GAL-SIA

Waters ×135

* Residue conservation analysis

PDB id:

1qdd

Name:

Metal binding protein

Title:

Crystal structure of human lithostathine to 1.3 a resolution

Structure:

Lithostathine. Chain: a. Synonym: pancreatic stone protein, psp. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

1.30Å R-factor: 0.132 R-free: 0.159

Authors:

V.Gerbaud,D.Pignol,E.Loret,J.A.Bertrand,Y.Berland,J.C.Fontecilla- Camps,J.P.Canselier,N.Gabas,J.M.Verdier

Key ref:

V.Gerbaud et al. (2000). Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine. J Biol Chem, 275, 1057-1064. PubMed id: 10625646 DOI: 10.1074/jbc.275.2.1057

Date:

20-May-99 Release date: 28-May-99

Protein chain

P05451  (REG1A_HUMAN) -  Lithostathine-1-alpha from Homo sapiens

Seq: 166 a.a.

Struc: 144 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1074/jbc.275.2.1057

J Biol Chem 275:1057-1064 (2000)

PubMed id: 10625646

Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.

V.Gerbaud, D.Pignol, E.Loret, J.A.Bertrand, Y.Berland, J.C.Fontecilla-Camps, J.P.Canselier, N.Gabas, J.M.Verdier.

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.

Selected figure(s)

Figure 1.
Fig. 1. A, ribbon diagram of the high resolution structure of human lithostathine produced with the program MOLSCRIPT (50). The elongated glycosylated N-terminal domain is in blue, and the C-type lectin domain is in cyan. B, view of the final (2Fo Fc) electron density map contoured at 1 around the O-glycosylation site of human lithostathine. The picture was drawn using the programs BOBSCRIPT (50, 51) and RASTER3D (52). NacGal, GalNAc.

Figure 3.
Fig. 3. Top views of the (10 4) (A) and (11 0) (B) faces of calcite. On the (10 4) face, the plane containing carbonate ions is parallel to the surface and always exhibits an O-C-O pattern, whereas on the (11 0) face, Y-shaped carbonate ions lie perpendicular to the surface, presenting alternately one or two oxygen atoms. Color codes are gray for carbon, red for oxygen, and blue for calcium atoms.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 1057-1064) copyright 2000.

Figures were selected by an automated process.