Modification of histidine (B10) is the causative agent for a superactive form of insulin.
The site of modification that is responsible for the formation of superactive insulin (ILM) was determined. The insulin derivative was prepared by treatment of insulin-Sepharose with ammonium bicarbonate. It was found that the insulin was bound to the resin through histidine B10, His (B10), and its ammonium bicarbonate-mediated release resulted in an insulin analog in which His (B10) was modified on the imidazole ring. This modification was reversible upon storage, resulting in normal levels of insulin activity. Amino acid analysis of a peptide containing this modified histidine revealed some aspartic acid. Since Asp (B10) insulin is also superactive, the observed superactivity may thus stem from either modification of the histidine or its conversion to aspartic acid.
Wilchek
Meir
M
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel. meir.wilchek@weizmann.ac.il
Miron
Talia
T
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000032:analysis; D001224:Aspartic Acid / Q000737:chemistry; D001639:Bicarbonates / Q000737:chemistry; D006639:Histidine / Q000737:chemistry*; D007328:Insulin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification; D012685:Sepharose / Q000737:chemistry; D013329:Structure-Activity Relationship
D000596:Amino Acids; D001639:Bicarbonates; D007328:Insulin; D001224:Aspartic Acid; C027043:ammonium bicarbonate; D006639:Histidine; D012685:Sepharose