PDBsum entry 1q8h

Metal binding protein

PDB id: 1q8h

Contents

Protein chain

37 a.a. *

Metals

_CA ×3

Waters ×61

* Residue conservation analysis

PDB id:

1q8h

Name:

Metal binding protein

Title:

Crystal structure of porcine osteocalcin

Structure:

Osteocalcin. Chain: a. Synonym: bone gla protein,bgp,gamma-carboxyglutamic acid-containing protein

Source:

Sus scrofa. Pig. Organism_taxid: 9823

Resolution:

2.00Å R-factor: 0.255 R-free: 0.283

Authors:

Q.Q.Hoang,F.Sicheri,A.J.Howard,D.S.Yang

Key ref:

Q.Q.Hoang et al. (2003). Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature, 425, 977-980. PubMed id: 14586470 DOI: 10.1038/nature02079

Date:

21-Aug-03 Release date: 11-Nov-03

Protein chain

Q8HYY9  (OSTCN_PIG) -  Osteocalcin from Sus scrofa

Seq: 49 a.a.

Struc: 37 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/nature02079

Nature 425:977-980 (2003)

PubMed id: 14586470

Bone recognition mechanism of porcine osteocalcin from crystal structure.

Q.Q.Hoang, F.Sicheri, A.J.Howard, D.S.Yang.

ABSTRACT

Osteocalcin is the most abundant noncollagenous protein in bone, and its concentration in serum is closely linked to bone metabolism and serves as a biological marker for the clinical assessment of bone disease. Although its precise mechanism of action is unclear, osteocalcin influences bone mineralization, in part through its ability to bind with high affinity to the mineral component of bone, hydroxyapatite. In addition to binding to hydroxyapatite, osteocalcin functions in cell signalling and the recruitment of osteoclasts and osteoblasts, which have active roles in bone resorption and deposition, respectively. Here we present the X-ray crystal structure of porcine osteocalcin at 2.0 A resolution, which reveals a negatively charged protein surface that coordinates five calcium ions in a spatial orientation that is complementary to calcium ions in a hydroxyapatite crystal lattice. On the basis of our findings, we propose a model of osteocalcin binding to hydroxyapatite and draw parallels with other proteins that engage crystal lattices.

Selected figure(s)

Figure 1.
Figure 1: Structure of pOC. a, Protein sequence with the secondary structure elements indicated and the conserved residues highlighted (green, red, blue, yellow, orange and grey indicate conserved, acidic, basic, cysteine, asparagine and glycine residues, respectively). Positions are identified as conserved if more than 85% of the residues are identical, or similar if hydrophobic in nature (see Supplementary Information for the full sequence alignment). ' ' indicates a Gla residue, open triangles and circles indicate hydrophobic core and Ca^2+-coordinating surface, respectively. b, Ribbon representation of the crystal structure. The N and C termini are labelled. Side chains of the Ca^2+-coordinating residues and those involved in tertiary structure stabilization are shown in stick representation. Broken grey line indicates a hydrogen bond. c, d, Molecular surface representations of pOC with the surface hydrophobic patch (green) and the Ca^2+-coordinating surface (red) highlighted. Views in b and c are perpendicular to that in d. e, Crystallographic dimer interface. Orange and blue distinguish the two molecules. Purple spheres and the yellow broken lines represent Ca^2+ ions and ionic bonds, respectively.

Figure 2.
Figure 2: Model of pOC engaging an HA crystal based on a Ca^2+ ion lattice match. Only the best search solution is shown (see Supplementary Information for a comparison of the four best solutions). a, Alignment of pOC-bound (purple) and HA (green) Ca^2+ ions. b, c, Orientation of pOC-bound Ca^2+ ions in a sphere of HA -Ca lattice (b) and on the HA surface (c). In b, the parallelogram indicates a unit cell; the box approximates the boundary of the slab shown in c and d. d, Docking of pOC (orange backbone with grey semitransparent surface) on HA. e, Detailed view of d showing the Ca -O coordination network at the pOC -HA interface. Yellow broken lines denote ionic bonds. Isolated red spheres and the tetrahedral clusters of magenta and red spheres represent OH- and PO[4]^3- ions, respectively.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 425, 977-980) copyright 2003.