1zlm

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[[Image:1zlm.gif|left|200px]]
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{{STRUCTURE_1zlm| PDB=1zlm | SCENE= }}
{{STRUCTURE_1zlm| PDB=1zlm | SCENE= }}
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'''Crystal structure of the SH3 domain of human osteoclast stimulating factor'''
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===Crystal structure of the SH3 domain of human osteoclast stimulating factor===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16946461 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16946461}}
==About this Structure==
==About this Structure==
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[[Category: Zhou, J.]]
[[Category: Zhou, J.]]
[[Category: Beta barrel]]
[[Category: Beta barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:46:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:26:30 2008''

Revision as of 21:26, 27 July 2008

Image:1zlm.png

Template:STRUCTURE 1zlm

Crystal structure of the SH3 domain of human osteoclast stimulating factor

Template:ABSTRACT PUBMED 16946461

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

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