Solution structure of a human calcitonin analog elucidated by NMR and distance geometry calculations.
Three-dimensional structure of a human calcitonin analog (abbreviated as hCTa) in which the amino acids of the wild type are replaced at position 12, 16 and 19 by leucine residues and further at position 22 by a tyrosine residue was studied in TFE solution by 1H-NMR and distance geometry calculations. This analog has a 15-20 times activity as compared with the wild type. The amino acid replacements resulted in formation of an amphiphilic alpha-helix in the region between the residues 4-20. The overall three-dimensional structure is similar to that of the wild type. The conformational feature of hCTa with a hydrophobic face composed with a Met and four Leu residues may be related to its higher hypocalcemic potency.
Katahira
R
R
International Research Laboratories, CIBA-Geigy Japan Ltd., Hyogo.
Doi
M
M
Kyogoku
Y
Y
Yamada-Nosaka
A
A
Yamasaki
K
K
Takai
M
M
Kobayashi
Y
Y
D000595:Amino Acid Sequence; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions
D012996:Solutions; D002116:Calcitonin