3sh4

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Revision as of 15:24, 11 August 2016

Laminin G like domain 3 from human perlecan

Structural highlights

3sh4 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3sh5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PGBM_HUMAN] Dyssegmental dysplasia, Silverman-Handmaker type;Schwartz-Jampel syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[PGBM_HUMAN] Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development. Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6. The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.

Publication Abstract from PubMed

Endorepellin, the C-terminal region of perlecan, inhibits angiogenesis by disrupting actin cytoskeleton and focal adhesions. The C-terminal laminin-like globular domain (LG3) of endorepellin directs most of this antiangiogenic activity. To investigate the angiostatic mechanism and to identify structural determinants, we have solved crystal structures of the LG3 domain in both apo- and calcium-bound forms at resolutions of 1.5 A and 2.8 A, respectively. The conserved core has the jellyroll fold characteristic of LG domains. The calcium-induced structural changes seem very restricted, and the calcium binding site appears to be preformed, suggesting that the bound calcium ion, rather than structural rearrangements, contributes to antiangiogenesis. We have identified H4268 on the EF loop as a key residue for the biochemical function of LG3, since its mutation abolishes antiangiogenic activity, and mutant LG3 can no longer form a direct interaction with integrin. Taken together, we propose that these two distinct structural elements contribute to the angiostatic effect of endorepellin.

Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor.,V Le B, Kim H, Choi J, Kim JH, Hahn MJ, Lee C, Kim KK, Hwang HY J Mol Biol. 2011 Nov 25;414(2):231-42. Epub 2011 Oct 4. PMID:21996443^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ V Le B, Kim H, Choi J, Kim JH, Hahn MJ, Lee C, Kim KK, Hwang HY. Crystal Structure of the LG3 Domain of Endorepellin, an Angiogenesis Inhibitor. J Mol Biol. 2011 Nov 25;414(2):231-42. Epub 2011 Oct 4. PMID:21996443 doi:10.1016/j.jmb.2011.09.048

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sh4"

@@ Line 1: / Line 1: @@
 ==Laminin G like domain 3 from human perlecan==
 <StructureSection load='3sh4' size='340' side='right' caption='[[3sh4]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3sh4]] is a 1 chain structure with 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=3SH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SH4 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sh5|3sh5]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sh4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sh4 RCSB], [http://www.ebi.ac.uk/pdbsum/3sh4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sh4 OCA], [http://pdbe.org/3sh4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sh4 RCSB], [http://www.ebi.ac.uk/pdbsum/3sh4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sh4 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/PGBM_HUMAN PGBM_HUMAN]] Dyssegmental dysplasia, Silverman-Handmaker type;Schwartz-Jampel syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/PGBM_HUMAN PGBM_HUMAN]] Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.  Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6.  The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3sh4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3sh4

From Proteopedia

Revision as of 15:24, 11 August 2016

Laminin G like domain 3 from human perlecan

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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