Screening of a phage display library of exendin-4 mutants with the extracellular domain of rat GLP-1 receptor.
A phage display library of exendin-4 mutants was screened with the extracellular domain of rat glucagon-like peptide 1 receptor as the target. A novel variant of exendin-4 with higher affinity for the receptor fraction than that of the wild type was identified. The increased affinity was attributed to the substitution of Glu(16) by Val(16). Although the substitution probably caused an increased entropic cost to the helix region, the linker around Val(16) is more flexible resulting in the increase of affinity for the receptor.
Yin
Xiaopu
X
State Key Laboratory of Bioreactor Engineering, Institute of Biochemistry, East China University of Science and Technology, Shanghai, PR China.
Ma
Yushu
Y
Liu
Meiyun
M
Gao
Weifeng
W
Wei
Dongzhi
D
D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D008969:Molecular Sequence Data; D009154:Mutation; D019151:Peptide Library; D010455:Peptides / Q000235:genetics*; D017434:Protein Structure, Tertiary; D051381:Rats; D018027:Receptors, Glucagon / Q000737:chemistry*; D014688:Venoms / Q000235:genetics*
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D019151:Peptide Library; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide