1huw

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{{STRUCTURE_1huw| PDB=1huw | SCENE= }}
 
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===THE CRYSTAL STRUCTURE OF AFFINITY-MATURED HUMAN GROWTH HORMONE AT 2 ANGSTROMS RESOLUTION===
 
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{{ABSTRACT_PUBMED_8107110}}
 
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==Disease==
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==THE CRYSTAL STRUCTURE OF AFFINITY-MATURED HUMAN GROWTH HORMONE AT 2 ANGSTROMS RESOLUTION==
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[[http://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN]] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:[http://omim.org/entry/262400 262400]]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH.<ref>PMID:8364549</ref> Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:[http://omim.org/entry/612781 612781]]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:[http://omim.org/entry/262650 262650]]; also known as pituitary dwarfism VI.<ref>PMID:8552145</ref><ref>PMID:9276733</ref><ref>PMID:17519310</ref> Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:[http://omim.org/entry/173100 173100]]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.
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<StructureSection load='1huw' size='340' side='right'caption='[[1huw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1huw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HUW FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1huw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1huw OCA], [https://pdbe.org/1huw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1huw RCSB], [https://www.ebi.ac.uk/pdbsum/1huw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1huw ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:[https://omim.org/entry/262400 262400]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH.<ref>PMID:8364549</ref> Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:[https://omim.org/entry/612781 612781]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:[https://omim.org/entry/262650 262650]; also known as pituitary dwarfism VI.<ref>PMID:8552145</ref> <ref>PMID:9276733</ref> <ref>PMID:17519310</ref> Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:[https://omim.org/entry/173100 173100]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.
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== Function ==
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[https://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hu/1huw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1huw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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==Function==
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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<ref>PMID:8107110</ref>
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[[http://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN]] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1huw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HUW OCA].
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</div>
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<div class="pdbe-citations 1huw" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:008107110</ref><ref group="xtra">PMID:009655339</ref><ref group="xtra">PMID:012215425</ref><references group="xtra"/><references/>
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*[[Human growth hormone|Human growth hormone]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kossiakoff, A A.]]
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[[Category: Large Structures]]
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[[Category: Somers, W S.]]
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[[Category: De Vos AM]]
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[[Category: Ultsch, M H.]]
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[[Category: Kossiakoff AA]]
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[[Category: Vos, A M.De.]]
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[[Category: Somers WS]]
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[[Category: Hormone]]
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[[Category: Ultsch MH]]

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

PDB ID 1huw

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