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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Xue J, Ray R, Singer D, Bohme D, Burz DS, Rai V, Hoffmann R, Shekhtman A. The Receptor for Advanced Glycation End Products (RAGE) Specifically Recognizes Methylglyoxal-Derived AGEs. Biochemistry. 2014 May 27;53(20):3327-35. doi: 10.1021/bi500046t. Epub 2014 May, 13. PMID:24824951 doi:http://dx.doi.org/10.1021/bi500046t
