Structure and activity of artificial mutant variants of human growth hormone.
Four artificial mutant variants of human growth hormone (hGH) with the following characteristics were prepared in Escherichia coli by in vitro mutagenesis: (i) replacement of Trp86 with Tyr (W86Y hGH); (ii) deletion of Trp86 (delta W86 hGH); (iii) deletion of residues 32-46 (20-kd-hGH); and (iv) deletion of residues 32-71 (17.5-kd-hGH). Both W86Y hGH and delta W86 hGH have a point mutation at Trp86 which is the only Trp residue in hGH and is conserved among members of the growth hormone family. 20-kd-hGH is a minor component of hGH in the pituitary gland and plasma and is the result of an alternative splicing of the primary gene transcript, while only the corresponding mRNA and not the protein has been found in the case of 17.5-kd-hGH. The biological activities (adipogenic activity and potentiation of gain in body weight) and structures (as analyzed by circular dichroism) were mostly retained by the W86Y, delta W86 and 20-kd-hGH variants but not by 17.5-kd-hGH.
Nishikawa
S
S
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nishida
Y
Y
Uemura
H
H
Yamada
Y
Y
Tanaka
T
T
Uesugi
S
S
Morikawa
M
M
Uchida
E
E
Hayakawa
T
T
Ikehara
M
M
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001835:Body Weight; D002942:Circular Dichroism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006062:Gonadotropins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D009154:Mutation; D051381:Rats; D014364:Tryptophan / Q000235:genetics
D006062:Gonadotropins; D014364:Tryptophan; D004247:DNA