Premium
Mutations in B‐type natriuretic peptide mediating receptor‐A selectivity
Author(s) -
Jill Schoenfeld,
Jeff Y.K. Tom,
David Lowe
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00956-3
Subject(s) - npr2 , natriuretic peptide , peptide , receptor , mutant , chemistry , atrial natriuretic peptide , medicine , npr1 , endocrinology , mutation , microbiology and biotechnology , biology , biochemistry , gene , heart failure
Libraries of monovalent display‐phage expressing mutant human B‐type natriuretic peptide (hBNP) were used to identify variants that preferentially bind natriuretic peptide receptor‐A (NPR‐A) compared to receptor‐C (NPR‐C). Position 19 was a significant determinant of receptor specificity for hBNP display phage. The synthetic hBNP variant S19R had a 265‐fold improved NPR‐A binding over NPR‐C, analogous to the atrial natriuretic peptide (ANP) specificity mutation G16R. Mutation of the last three residues of the hBNP disulfide ring, G23F/L24W/G25R, resulted in about 9‐fold improved selectivity. The analogous mutations in ANP decreased NPR‐A binding, suggesting divergence in the mechanism of NPR‐A recognition.