1HUW

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

Summary for 1HUW

• Entry DOI: 10.2210/pdb1huw/pdb
• Descriptor: HUMAN GROWTH HORMONE (2 entities in total)
• Functional Keywords: hormone
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01241
• Total number of polymer chains: 1
• Total formula weight: 21986.63

Authors

Ultsch, M.H.,Somers, W.S.,Kossiakoff, A.A.,De Vos, A.M. (deposition date: 1993-09-22, release date: 1994-01-31, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)