View source for 1zlm


==Crystal structure of the SH3 domain of human osteoclast stimulating factor==
<StructureSection load='1zlm' size='340' side='right'caption='[[1zlm]], [[Resolution|resolution]] 1.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zlm]] is a 1 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZLM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.07&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlm OCA], [https://pdbe.org/1zlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zlm RCSB], [https://www.ebi.ac.uk/pdbsum/1zlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OSTF1_HUMAN OSTF1_HUMAN] Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.<ref>PMID:10092216</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zl/1zlm_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zlm ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:16946461</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1zlm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen L]]
[[Category: DiGiammarino E]]
[[Category: Harold H]]
[[Category: Meehan EJ]]
[[Category: Toh D]]
[[Category: Wang Y]]
[[Category: Wells D]]
[[Category: Zhou J]]