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| | <StructureSection load='1h02' size='340' side='right'caption='[[1h02]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1h02' size='340' side='right'caption='[[1h02]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1h02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. The April 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Growth Hormone'' by Shuchismita Dutta and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_4 10.2210/rcsb_pdb/mom_2004_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1h02]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Growth Hormone'' by Shuchismita Dutta and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_4 10.2210/rcsb_pdb/mom_2004_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H02 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gzr|1gzr]], [[1gzy|1gzy]], [[1gzz|1gzz]], [[1h59|1h59]], [[1imx|1imx]], [[2gf1|2gf1]], [[3gf1|3gf1]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C15:N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE'>C15</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h02 OCA], [https://pdbe.org/1h02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h02 RCSB], [https://www.ebi.ac.uk/pdbsum/1h02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h02 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h02 OCA], [https://pdbe.org/1h02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h02 RCSB], [https://www.ebi.ac.uk/pdbsum/1h02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h02 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN]] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:[https://omim.org/entry/608747 608747]]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
| + | [https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN] Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:[https://omim.org/entry/608747 608747]. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN]] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.<ref>PMID:21076856</ref>
| + | [https://www.uniprot.org/uniprot/IGF1_HUMAN IGF1_HUMAN] The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.<ref>PMID:21076856</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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Line 39: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Growth Hormone]] | | [[Category: Growth Hormone]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Bree, F M.De]] | + | [[Category: Brzozowski AM]] |
| - | [[Category: Brzozowski, A M]] | + | [[Category: Dauter Z]] |
| - | [[Category: Dauter, Z]] | + | [[Category: De Bree FM]] |
| - | [[Category: Dodson, E J]] | + | [[Category: Dodson EJ]] |
| - | [[Category: Dodson, G G]] | + | [[Category: Dodson GG]] |
| - | [[Category: Murshudov, G]] | + | [[Category: Murshudov G]] |
| - | [[Category: Turkenburg, J P]] | + | [[Category: Turkenburg JP]] |
| - | [[Category: Verma, C]] | + | [[Category: Verma C]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Growth factor]]
| + | |
| - | [[Category: Igf-1]]
| + | |
| - | [[Category: Insulin family]]
| + | |
| - | [[Category: Plasma]]
| + | |
| Structural highlights
Disease
IGF1_HUMAN Defects in IGF1 are the cause of insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747. IGF1 deficiency is an autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
Function
IGF1_HUMAN The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in rat bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human insulin-like growth factors I and II (hIGF-I, hIGF-II) are potent stimulators of cell and growth processes. They display high sequence similarity to both the A and B chains of insulin but contain an additional connecting C-domain, which reflects their secretion without specific packaging or precursor conversion. IGFs also have an extension at the C-terminus known as the D-domain. This paper describes four homologous hIGF-1 structures, obtained from crystals grown in the presence of the detergent SB12, which reveal additional detail in the C- and D-domains. Two different detergent binding modes observed in the crystals may reflect different hIGF-I biological properties such as the interaction with IGF binding proteins and self-aggregation. While the helical core of hIGF-I is very similar to that in insulin, there are distinct differences in the region of hIGF-I corresponding to the insulin B chain C-terminus, residues B25-B30. In hIGF-I, these residues (24-29) and the following C-domain form an extensive loop protruding 20 A from the core, which results in a substantially different conformation for the receptor binding epitope in hIGF-I compared to insulin. One notable feature of the structures presented here is demonstration of peptide-bond cleavage between Ser35 and Arg36 resulting in an apparent gap between residues 35 and 39. The equivalent region of proinsulin is involved in hormone processing demanding a reassessment of the structural integrity of hIGF-I in relation to its biological function.
Structural origins of the functional divergence of human insulin-like growth factor-I and insulin.,Brzozowski AM, Dodson EJ, Dodson GG, Murshudov GN, Verma C, Turkenburg JP, de Bree FM, Dauter Z Biochemistry. 2002 Jul 30;41(30):9389-97. PMID:12135360[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zoidis E, Ghirlanda-Keller C, Schmid C. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I. Mol Cell Biochem. 2011 Feb;348(1-2):33-42. doi: 10.1007/s11010-010-0634-z. Epub, 2010 Nov 13. PMID:21076856 doi:10.1007/s11010-010-0634-z
- ↑ Brzozowski AM, Dodson EJ, Dodson GG, Murshudov GN, Verma C, Turkenburg JP, de Bree FM, Dauter Z. Structural origins of the functional divergence of human insulin-like growth factor-I and insulin. Biochemistry. 2002 Jul 30;41(30):9389-97. PMID:12135360
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