1huw
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THE CRYSTAL STRUCTURE OF AFFINITY-MATURED HUMAN GROWTH HORMONE AT 2 ANGSTROMS RESOLUTION
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Growth hormone deficiency OMIM:[139250], Growth hormone deficiency, isolated, type IA OMIM:[139250], Growth hormone deficiency, isolated, type IB OMIM:[139250], Growth hormone deficiency, isolated, type II OMIM:[139250], Kowarski syndrome OMIM:[139250], Short stature, familial OMIM:[139250]
About this StructureAbout this Structure
1HUW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of affinity-matured human growth hormone at 2 A resolution., Ultsch MH, Somers W, Kossiakoff AA, de Vos AM, J Mol Biol. 1994 Feb 11;236(1):286-99. PMID:8107110
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