Sandbox Reserved 1657: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
<scene name='86/868190/5czx_version_2_with_ligands/1'>5CZX</scene> stands for the <scene name='86/868190/Nrr_domain_alonecentre/4'>NRR (negative regulatory region)</scene> of the [https://www.uniprot.org/uniprot/Q9UM47 neurogenic locus notch homolog protein 3] in complex with 20358 [https://en.wikipedia.org/wiki/Fragment_antigen-binding Fab]. This NRR is made of <scene name='86/868190/4zlp_2_chains_nrr/1'>2 identical chain structures</scene> encoded by the [https://en.wikipedia.org/wiki/Notch_3 NOTCH3 gene](In this article, we will only focus on one of the two chains). It is composed of <scene name='86/868190/Lnr_domains/1'>three LIN12/Notch repeats and linker</scene> (LNRs respectively <scene name='86/868190/Lna_domain/1'>LNR-A</scene>,<scene name='86/868190/Lnb_domain/1'>LNR-B</scene>, <scene name='86/868190/Lrn_linker_bc/1'>LNR-B/C linker</scene> and <scene name='86/868190/Lnc/1'>LNR-C</scene> ) and a <scene name='86/868190/Hd/1'>heterodimerization domain (HD)</scene> composed by <scene name='86/868190/Hd-c/1'>HD-C</scene> and <scene name='86/868190/Hd-n/1'>HD-N</scene>.<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref>. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5czx OCA]. For a guided tour on the structure components in complex with [https://swissmodel.expasy.org/templates/5czx.2 20358 Fab] use [https://proteopedia.org/wiki/fgij/fg.htm?mol=5CZX FirstGlance]. | <scene name='86/868190/5czx_version_2_with_ligands/1'>5CZX</scene> stands for the <scene name='86/868190/Nrr_domain_alonecentre/4'>NRR (negative regulatory region)</scene> of the [https://www.uniprot.org/uniprot/Q9UM47 neurogenic locus notch homolog protein 3] in complex with 20358 [https://en.wikipedia.org/wiki/Fragment_antigen-binding Fab]. This NRR is made of <scene name='86/868190/4zlp_2_chains_nrr/1'>2 identical chain structures</scene> encoded by the [https://en.wikipedia.org/wiki/Notch_3 NOTCH3 gene](In this article, we will only focus on one of the two chains). It is composed of <scene name='86/868190/Lnr_domains/1'>three LIN12/Notch repeats and linker</scene> (LNRs respectively <scene name='86/868190/Lna_domain/1'>LNR-A</scene>,<scene name='86/868190/Lnb_domain/1'>LNR-B</scene>, <scene name='86/868190/Lrn_linker_bc/1'>LNR-B/C linker</scene> and <scene name='86/868190/Lnc/1'>LNR-C</scene> ) and a <scene name='86/868190/Hd/1'>heterodimerization domain (HD)</scene> composed by <scene name='86/868190/Hd-c/1'>HD-C</scene> and <scene name='86/868190/Hd-n/1'>HD-N</scene>.<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref>. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5czx OCA]. For a guided tour on the structure components in complex with [https://swissmodel.expasy.org/templates/5czx.2 20358 Fab] use [https://proteopedia.org/wiki/fgij/fg.htm?mol=5CZX FirstGlance]. | ||
The X-Ray crystallized structure 5CZX was realized and published in the same article (Article reference<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref>) as [https://www.rcsb.org/structure/5CZV 5CZV] (Notch 3 NRR in complex with 20350) in order to exhibit the areas of the NRR bound by the studied antibody and draw conclusions regarding their Notch3 signalling inhibitory properties. | |||
MOR 20358 is an Anti-Human Notch 3 recombinant antibody designed for therapeutic purpose in the curing of the T-Cell Acute lymphoblastic leukemia disease. | |||
The study<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref> has provided evidence that MOR 20358 binds to half of the LRN-C linker and parts of the HD-C and the LNR-B/C domains, which would therefore lock the Notch 3 NRR in an auto-inhibitory conformation, ending up inhibiting the Notch signalling. This property may constitute a treatment in cases of Notch3 over-activation related cancers. | |||
<table><tr><td colspan='3'><br> | <table><tr><td colspan='3'><br> | ||
