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New page: left|200px<br /> <applet load="1vsc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vsc, resolution 1.9Å" /> '''VCAM-1'''<br /> ==O...
 
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'''VCAM-1'''<br />


==Overview==
==VCAM-1==
Vascular cell adhesion molecule 1 (VCAM-1) represents a structurally and, functionally distinct class of immunoglobulin superfamily molecules that, bind leukocyte integrins and are involved in inflammatory and immune, functions. X-ray crystallography defines the three-dimensional structure, of the N-terminal two-domain fragment that participates in ligand binding., Residues in domain 1 important for ligand binding reside in the C-D loop, which projects markedly from one face of the molecule near the contact, between domains 1 and 2. A cyclic peptide that mimics this loop inhibits, binding of alpha 4 beta 1 integrin-bearing cells to VCAM-1. These data, demonstrate how crystallographic structural information can be used to, design a small molecule inhibitor of biological function.
<StructureSection load='1vsc' size='340' side='right'caption='[[1vsc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1vsc]] is a 2 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=1VSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VSC 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]] 1.9&#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=1vsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vsc OCA], [https://pdbe.org/1vsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vsc RCSB], [https://www.ebi.ac.uk/pdbsum/1vsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vsc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VCAM1_HUMAN VCAM1_HUMAN] Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with the beta-1 integrin VLA4 on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/VLA4 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
== 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/vs/1vsc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1vsc ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Vascular cell adhesion molecule 1 (VCAM-1) represents a structurally and functionally distinct class of immunoglobulin superfamily molecules that bind leukocyte integrins and are involved in inflammatory and immune functions. X-ray crystallography defines the three-dimensional structure of the N-terminal two-domain fragment that participates in ligand binding. Residues in domain 1 important for ligand binding reside in the C-D loop, which projects markedly from one face of the molecule near the contact between domains 1 and 2. A cyclic peptide that mimics this loop inhibits binding of alpha 4 beta 1 integrin-bearing cells to VCAM-1. These data demonstrate how crystallographic structural information can be used to design a small molecule inhibitor of biological function.


==Disease==
The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction.,Wang JH, Pepinsky RB, Stehle T, Liu JH, Karpusas M, Browning B, Osborn L Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5714-8. PMID:7539925<ref>PMID:7539925</ref>
Known diseases associated with this structure: CRASH syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]], Corpus callosum, partial agenesis of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]], Hydrocephalus due to aqueductal stenosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]], Hydrocephalus with Hirschsprung disease and cleft palate OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]], Hydrocephalus with congenital idiopathic intestinal pseudoobstruction OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]], MASA syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=308840 308840]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1VSC 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VSC OCA].
</div>
 
<div class="pdbe-citations 1vsc" style="background-color:#fffaf0;"></div>
==Reference==
== References ==
The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction., Wang JH, Pepinsky RB, Stehle T, Liu JH, Karpusas M, Browning B, Osborn L, Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5714-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7539925 7539925]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Osborn, L.]]
[[Category: Osborn L]]
[[Category: Stehle, T.]]
[[Category: Stehle T]]
[[Category: Wang, J.]]
[[Category: Wang J]]
[[Category: cell adhesion protein]]
[[Category: glycoprotein]]
[[Category: immunoglobulin fold]]
 
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Latest revision as of 07:40, 23 October 2024

VCAM-1

1vsc, resolution 1.90Å

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