PDBsum entry 1zlm

Signaling protein

PDB id: 1zlm

Contents

Protein chain

58 a.a. *

Waters ×130

* Residue conservation analysis

PDB id:

1zlm

Name:

Signaling protein

Title:

Crystal structure of the sh3 domain of human osteoclast stimulating factor

Structure:

Osteoclast stimulating factor 1. Chain: a. Fragment: sh3 domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ostf1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.07Å R-factor: 0.160 R-free: 0.212

Authors:

L.Chen,Y.Wang,D.Wells,D.Toh,H.Harold,J.Zhou,E.Digiammarino,E.J.Meehan

Key ref:

L.Chen et al. (2006). Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 844-848. PubMed id: 16946461 DOI: 10.1107/S1744309106030004

Date:

06-May-05 Release date: 16-May-06

Protein chain

Q92882  (OSTF1_HUMAN) -  Osteoclast-stimulating factor 1 from Homo sapiens

Seq: 214 a.a.

Struc: 58 a.a.

DOI no: 10.1107/S1744309106030004

Acta Crystallogr Sect F Struct Biol Cryst Commun 62:844-848 (2006)

PubMed id: 16946461

Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution.

L.Chen, Y.Wang, D.Wells, D.Toh, H.Harold, J.Zhou, E.DiGiammarino, E.J.Meehan.

ABSTRACT

Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein-protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12-72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 A. The overall structure shows a characteristic SH3 fold consisting of two perpendicular beta-sheets that form a beta-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors.

Selected figure(s)

Figure 2.
Structure-based sequence alignment of hOSF-SH3 with the most similar SH3 domains. The sequence numbers for the first and the last residues are indicated. The positions of the [beta]-strands in hOSF-SH3 are indicated by underlining the sequence and are labeled. Residues that are highly conserved in the SH3-domain family are indicated in bold type. Residues that are known to form the proline-rich ligand-binding pocket are marked with an asterisk. See Table 2 [triangle] for protein PDB codes and references. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 September 1; 62(Pt 9): 844. Published online 2006 August 18. doi: 10.1107/S1744309106030004. Copyright [copyright] International Union of Crystallography 2006

Figure 3.
Structure comparison and the peptide-binding model. Stereoview of structural superposition of hOSF-SH3 (black) with c-Crk-SH3 (red; PDB code 1cka) in complex with the proline-rich peptide PPPALPPKK (green). Residues involved in peptide binding are shown as stick models and the rest as C^[alpha] traces. The peptide is also shown with stick models. For clarity, only the termini and the key residues of hOSF-SH3 are labeled. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 September 1; 62(Pt 9): 844. Published online 2006 August 18. doi: 10.1107/S1744309106030004. Copyright [copyright] International Union of Crystallography 2006

The above figures are reprinted from an Open Access publication published by the IUCr: Acta Crystallogr Sect F Struct Biol Cryst Commun (2006, 62, 844-848) copyright 2006.

Figures were selected by an automated process.