Insulin-like growth factor receptor

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<StructureSection load='3nw6' size='400' side='right' caption='Structure of IGFR I kinase domain complex with inhibitor (PDB entry [[3nw6]])' scene=''>
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<StructureSection load='3i81' size='350' side='right' scene='' caption='Human insulin-like growth factor 1 receptor complex with inhibitor (PDB code [[3i81]])'>
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'''Insulin-like growth factor receptors''' (IGFR) are transmembrane receptors which are stimulated by insulin-like growth factors (IGF). IGFR contains 2 extracellular α chains and 2 transmembranal β chains. Upon binding of IGF, a tyrosine in the β chain becomes autophosphorylated and triggers a cascade of intracellular signaling. The insulin-like growth factor 1 (IGF-1) receptor belongs to the large class of [[Receptor tyrosine kinases|tyrosine kinase receptors]]. See also [[IGF1]], [[Growth factors]] and [[Kinase-linked, enzyme-linked and related receptors]].
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*'''Insulin-like growth factor receptor 1''' is the mediator of the anabolic and mitogenic activity of growth hormone<ref>PMID: 11577173</ref><br />
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*'''Insulin-like growth factor receptor 2''' is a protein hormone regulating cell proliferation, growth, migration, differentiation and survival<ref>PMID: 23257688</ref><br />.
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=== Memory-Enhancement by Traditional Chinese Medicine? <ref>doi 10.1080/07391102.2012.741052</ref>===
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'''Insulin-like growth factor receptors''' (IGFR) are transmembrane receptors which are stimulated by insulin-like growth factors (IGF). IGFR contains 2 extracellular α chains and 2 transmembranal β chains. Upon binding of IGF, a tyrosine in the β chain becomes autophosphorylated and triggers a cascade of intracellular signaling.
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Cognitive impairment is an emerging issue and increasing research points to the significant role of insulin-like growth factor I (IGF-I) in cognitive brain functions. <scene name='Journal:JBSD:38/Cv/3'>IGF receptor </scene> (IGF-IR, PDB ID: [[3i81]], <font color='darkmagenta'><b>colored in darkmagenta</b></font>) activation is critical for IGF-I to elicit desirable cognitive functions. Traditional Chinese medicine (TCM) ligands <scene name='Journal:JBSD:38/Cv/2'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> (orgin: ''Isatisin digotica'', <span style="color:lime;background-color:black;font-weight:bold;">colored in green</span>), <scene name='Journal:JBSD:38/Cv/4'>(+)-N-methyllaurotetanine</scene> (origin: ''Lindera aggregate'', <span style="color:deeppink;background-color:black;font-weight:bold;">colored in deeppink</span>), and <scene name='Journal:JBSD:38/Cv/5'>(+)-1(R)-Coclaurine</scene> (origin: ''Nelumbonucifera Gaertn'', <span style="color:salmon;background-color:black;font-weight:bold;">colored in salmon</span>) showed high binding affinity towards IGF-IR at the binding site defined by the control in PDB ID: [[3i81]]. Molecular dynamics simulation revealed that the TCM ligands were secured at the opening of the IGF-IR binding site for the duration of the MD. <scene name='Journal:JBSD:38/Cv/7'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/8'>Asp1056</scene>, <scene name='Journal:JBSD:38/Cv/9'>(+)-N-methyllaurotetanine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/10'>Leu975 and Asp1056</scene>, and <scene name='Journal:JBSD:38/Cv/11'>(+)-1(R)-Coclaurine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/12'>Leu975 and Gly1055</scene> (<span style="color:yellow;background-color:black;font-weight:bold;">key residues are colored in yellow</span>). Four different quantitative-structure activity relationship models consistently predicted bioactivity of the TCM ligands towards IGF-IR. In summary, the TCM candidates exhibit drug-like potential in both structural-based and ligand-based properties and may have potential for further applications in enhancing cognition.
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</StructureSection>
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__NOTOC__
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===3D structures of insulin-like growth factor receptor===
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==3D structures of insulin-like growth factor receptor==
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==IGFR I==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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[[1igr]] – hIGFR I domains 1-3 – human<BR />
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*IGFR I
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[[2cnj]] - hIGFR I domain 11 - NMR<BR />
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[[1q25]] - bIGFR I domains 1-3 – bovine<BR />
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[[1jqh]], [[1p4o]] - hIGFR I kinase domain (mutant) <BR />
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[[1m7n]] - hIGFR I kinase domain<BR />
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[[1k3a]] - hIGFR I kinase domain + insulin receptor substrate peptide<BR />
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[[2oj9]], [[2zm3]], [[3d94]], [[3f5p]], [[3i81]], [[3lvp]], [[3nw5]], [[3nw6]], [[3nw7]], [[3lw0]], [[3qqu]], [[3o23]] - hIGFR I kinase domain + inhibitor<BR />
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[[1syo]], [[1sz0]] - bIGFR I domains 1-3 + mannose-6-phosphate<BR />
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==IGFR II==
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**[[1igr]] – hIGFR I domains 1-3 31-492– human<BR />
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**[[1jqh]], [[1p4o]] - hIGFR I kinase domain (mutant) 983-1286<BR />
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**[[1m7n]] - hIGFR I kinase domain<BR />
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**[[1k3a]] - hIGFR I kinase domain + insulin receptor substrate peptide<BR />
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**[[2oj9]], [[2zm3]], [[3d94]], [[3f5p]], [[3i81]], [[3lvp]], [[3nw5]], [[3nw6]], [[3nw7]], [[3lw0]], [[3qqu]], [[3o23]], [[4d2r]], [[5fxq]], [[5fxr]], [[5fxs]], [[5hzn]] - hIGFR I kinase domain + inhibitor<BR />
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**[[5u8r]] - hIGFR I (mutant) + antibody<BR />
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**[[5u8q]] - hIGFR I (mutant) + IGFI + antibody<BR />
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**[[6pyh]] - hIGFR I + IGFI – Cryo EM<BR />
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**[[6vwg]], [[6vwh]], [[6vwi]], [[6vwj]] - hIGFR I + IGFII – Cryo EM<BR />
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**[[7s8v]] - hIGFR I + insulin receptor – Cryo EM<BR />
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**[[7s0q]] - hIGFR I + insulin receptor + IGF I – Cryo EM<BR />
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[[1gqb]] - hIGFR II<BR />
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*IGFR II
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[[2kva]] - hIGFR II domain 5 – NMR<BR />
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[[2l2a]] - hIGFR II domains 11 (mutant) - NMR<BR />
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[[2kvb]] - hIGFR II domain 5 + inhibitor – NMR<BR />
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[[2v5n]] - hIGFR II domains 11-12<BR />
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[[2v5o]] - hIGFR II domains 11-14<BR />
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[[2v5p]] - hIGFR II domains 11-13 + IGF II<BR />
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[[2l29]] - hIGFR II domain 11 + IGF II - NMR<BR />
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[[1gp0]], [[1gp3]], [[1e6f]] - hIGFR II IGF II-binding domain
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**[[1gqb]] - hIGFR II<BR />
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**[[2kva]] - hIGFR II domain 5 – NMR<BR />
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**[[2cnj]] - hIGFR II domain 11 - NMR<BR />
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**[[2l2a]], [[2m68]], [[2m6t]] - hIGFR II domains 11 (mutant) - NMR<BR />
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**[[2kvb]] - hIGFR II domain 5 + inhibitor – NMR<BR />
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**[[2v5n]] - hIGFR II domains 11-12<BR />
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**[[2v5o]] - hIGFR II domains 11-14<BR />
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**[[2v5p]] - hIGFR II domains 11-13 + IGF II<BR />
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**[[2l29]] - hIGFR II domain 11 + IGF II - NMR<BR />
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**[[1gp0]], [[1gp3]], [[1e6f]] - hIGFR II IGF II-binding domain<br />
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**[[1q25]] - bIGFR II domains 1-3 – bovine<BR />
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**[[1syo]], [[1sz0]] - bIGFR II domains 1-3 + mannose-6-phosphate<BR />
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**[[2lla]] - IGFR II domain 11 – short-beaked echidna - NMR<BR />
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**[[2l2g]] - IGFR II domain 11 – opossum - NMR<BR />
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}}
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human insulin-like growth factor 1 receptor complex with inhibitor (PDB code 3i81)

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3D structures of insulin-like growth factor receptor

Updated on 03-July-2024

References

  1. ↑ Laron Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol. 2001 Oct;54(5):311-6. PMID:11577173
  2. ↑ Bergman D, Halje M, Nordin M, Engström W. Insulin-like growth factor 2 in development and disease: a mini-review. Gerontology. 2013;59(3):240-9. PMID:23257688 doi:10.1159/000343995
  3. ↑ Hung IC, Chang SS, Chang PC, Lee CC, Chen CY. Memory enhancement by traditional Chinese medicine? J Biomol Struct Dyn. 2012 Dec 19. PMID:23249175 doi:10.1080/07391102.2012.741052

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Michal Harel, Alexander Berchansky

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