View source for 2mov


==Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal Derived AGEs.==
<StructureSection load='2mov' size='340' side='right'caption='[[2mov]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mov]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MOV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOR:N~5~-[(5R)-5-METHYL-4-OXO-4,5-DIHYDRO-1H-IMIDAZOL-2-YL]-L-ORNITHINE'>IOR</scene></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=2mov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mov OCA], [https://pdbe.org/2mov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mov RCSB], [https://www.ebi.ac.uk/pdbsum/2mov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mov ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAGE_HUMAN RAGE_HUMAN] Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.<ref>PMID:19906677</ref> 
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== Publication Abstract from PubMed ==
Diabetes-induced hyperglycemia increases the extracellular concentration of methylglyoxal. Methylglyoxal-derived hydroimidazolones (MG-H) form advanced glycation end products (AGEs) that accumulate in the serum of diabetic patients. The binding of hydroimidozolones to the receptor for AGEs (RAGE) results in long-term complications of diabetes typified by vascular and neuronal injury. Here we show that binding of methylglyoxal-modified albumin to RAGE results in signal transduction. Chemically synthesized peptides containing hydroimidozolones bind specifically to the V domain of RAGE with nanomolar affinity. The solution structure of an MG-H1-V domain complex revealed that the hydroimidazolone moiety forms multiple contacts with a positively charged surface on the V domain. The high affinity and specificity of hydroimidozolones binding to the V domain of RAGE suggest that they are the primary AGE structures that give rise to AGEs-RAGE pathologies.

The Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal-Derived AGEs.,Xue J, Ray R, Singer D, Bohme D, Burz DS, Rai V, Hoffmann R, Shekhtman A Biochemistry. 2014 May 27;53(20):3327-35. doi: 10.1021/bi500046t. Epub 2014 May, 13. PMID:24824951<ref>PMID:24824951</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 2mov" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bohme D]]
[[Category: Burz DS]]
[[Category: Hoffman R]]
[[Category: Rai V]]
[[Category: Ray R]]
[[Category: Shekhtman A]]
[[Category: Singer D]]
[[Category: Xue J]]