1huw
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1huw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1huw OCA], [http://www.ebi.ac.uk/pdbsum/1huw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1huw RCSB]</span> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Growth hormone deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IB OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Kowarski syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Short stature, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: hormone]] | [[Category: hormone]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:10:46 2008'' |
Revision as of 18:10, 30 March 2008
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| , resolution 2.0Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE CRYSTAL STRUCTURE OF AFFINITY-MATURED HUMAN GROWTH HORMONE AT 2 ANGSTROMS RESOLUTION
Overview
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.
About this Structure
1HUW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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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