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1zlm
From Proteopedia
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| , resolution 1.07Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | OSTF1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the SH3 domain of human osteoclast stimulating factor
Overview
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.
About this Structure
1ZLM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the SH3 domain of human osteoclast-stimulating factor at atomic resolution., Chen L, Wang Y, Wells D, Toh D, Harold H, Zhou J, DiGiammarino E, Meehan EJ, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Sep 1;62(Pt, 9):844-8. Epub 2006 Aug 18. PMID:16946461
Page seeded by OCA on Mon Mar 31 01:38:22 2008
Categories: Homo sapiens | Single protein | Chen, L. | DiGiammarino, E. | Harold, H. | Meehan, E J. | Toh, D. | Wang, Y. | Wells, D. | Zhou, J. | Beta barrel
