1ZLM

Crystal structure of the SH3 domain of human osteoclast stimulating factor

Summary for 1ZLM

• Entry DOI: 10.2210/pdb1zlm/pdb
• Descriptor: Osteoclast stimulating factor 1 (2 entities in total)
• Functional Keywords: beta barrel, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Probable): Q92882
• Total number of polymer chains: 1
• Total formula weight: 6741.46

Authors

Chen, L.,Wang, Y.,Wells, D.,Toh, D.,Harold, H.,Zhou, J.,DiGiammarino, E.,Meehan, E.J. (deposition date: 2005-05-06, release date: 2006-05-16, Last modification date: 2023-08-23)

Primary citation

Chen, L.,Wang, Y.,Wells, D.,Toh, D.,Harold, H.,Zhou, J.,DiGiammarino, E.,Meehan, E.J.
Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution.
Acta Crystallogr.,Sect.F, 62:844-848, 2006

PubMed 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.

PubMed: 16946461
DOI: 10.1107/S1744309106030004

Experimental method

X-RAY DIFFRACTION (1.07 Å)