1HUW

THE CRYSTAL STRUCTURE OF AFFINITY-MATURED HUMAN GROWTH HORMONE AT 2 ANGSTROMS RESOLUTION

1HUW の概要

• エントリーDOI: 10.2210/pdb1huw/pdb
• 分子名称: HUMAN GROWTH HORMONE (2 entities in total)
• 機能のキーワード: hormone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01241
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21986.63

構造登録者

Ultsch, M.H.,Somers, W.S.,Kossiakoff, A.A.,De Vos, A.M. (登録日: 1993-09-22, 公開日: 1994-01-31, 最終更新日: 2024-10-23)

主引用文献

Ultsch, M.H.,Somers, W.,Kossiakoff, A.A.,de Vos, A.M.
The crystal structure of affinity-matured human growth hormone at 2 A resolution.
J.Mol.Biol., 236:286-299, 1994

PubMed Abstract: A variant of human growth hormone (hGH), in which 15 mutations were introduced with phage display mutagenesis to improve receptor binding affinity by 400-fold, yielded two related crystal forms diffracting to high resolution. The structure of this variant was determined in both crystal forms, one at 2.0 A resolution and one at 2.4 A resolution, using molecular replacement with wild-type hGH taken from the receptor complex structure as a search model. Crystallographic refinement of the 2 A structure gave an R-value R-value of 18.5% for data in the resolution range 8 to 2 A. The final model consists of residues 1 to 128 and 155 to 191, with three side-chains modeled in alternative conformations, together with 77 water molecules. Comparison of the structure with wild-type hGH shows that most of the secondary structural elements are unchanged. The exception is the first turn of the third helix in the four-helix bundle core, which is unraveled in the present variant. Analysis of the two related packing environments suggests that this change is caused by crystal packing forces. A large change in the orientation of a short segment of helix found in the connection between the first two core helices is interpreted as evidence for rigid-body variability of this helical segment. Analysis of the mutations in light of the structure of the wild-type hGH/receptor complex shows that six of the mutations are buried in the hormone, whereas the remaining nine involve residues that interact with the receptor in the complex.

PubMed: 8107110
DOI: 10.1006/jmbi.1994.1135

実験手法

X-RAY DIFFRACTION (2 Å)