2MOV

Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal Derived AGEs.

2MOV の概要

• エントリーDOI: 10.2210/pdb2mov/pdb
• NMR情報: BMRB: 19953
• 分子名称: Advanced glycosylation end product-specific receptor, N~5~-[(5R)-5-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl]-L-ornithine (2 entities in total)
• 機能のキーワード: protein/ligand, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: Q15109
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11799.57

構造登録者

Shekhtman, A.,Xue, J.,Ray, R.,Singer, D.,Bohme, D.,Burz, D.S.,Rai, V.,Hoffman, R. (登録日: 2014-05-05, 公開日: 2014-06-25, 最終更新日: 2024-10-30)

主引用文献

Xue, J.,Ray, R.,Singer, D.,Bohme, D.,Burz, D.S.,Rai, V.,Hoffmann, R.,Shekhtman, A.
The Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal-Derived AGEs.
Biochemistry, 53:3327-3335, 2014

PubMed Abstract: 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.

PubMed: 24824951
DOI: 10.1021/bi500046t

実験手法

SOLUTION NMR