1zlm
From Proteopedia
(New page: 200px<br /> <applet load="1zlm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zlm, resolution 1.07Å" /> '''Crystal structure o...) |
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| - | [[Image:1zlm.gif|left|200px]]<br /> | + | [[Image:1zlm.gif|left|200px]]<br /><applet load="1zlm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zlm" size=" | + | |
caption="1zlm, resolution 1.07Å" /> | caption="1zlm, resolution 1.07Å" /> | ||
'''Crystal structure of the SH3 domain of human osteoclast stimulating factor'''<br /> | '''Crystal structure of the SH3 domain of human osteoclast stimulating factor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and | + | 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== | ==About this Structure== | ||
| - | 1ZLM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ZLM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZLM OCA]. |
==Reference== | ==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 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16946461 16946461] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: DiGiammarino, E.]] | [[Category: DiGiammarino, E.]] | ||
[[Category: Harold, H.]] | [[Category: Harold, H.]] | ||
| - | [[Category: Meehan, E | + | [[Category: Meehan, E J.]] |
[[Category: Toh, D.]] | [[Category: Toh, D.]] | ||
[[Category: Wang, Y.]] | [[Category: Wang, Y.]] | ||
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[[Category: beta barrel]] | [[Category: beta barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:46 2008'' |
Revision as of 14:16, 21 February 2008
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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 Thu Feb 21 16:16:46 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
