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| | <StructureSection load='6a78' size='340' side='right'caption='[[6a78]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='6a78' size='340' side='right'caption='[[6a78]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6a78]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A78 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A78 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6a78]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A78 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ROBO1, DUTT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6a78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a78 OCA], [http://pdbe.org/6a78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a78 RCSB], [http://www.ebi.ac.uk/pdbsum/6a78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a78 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=6a78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a78 OCA], [https://pdbe.org/6a78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a78 RCSB], [https://www.ebi.ac.uk/pdbsum/6a78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a78 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ROBO1_HUMAN ROBO1_HUMAN]] Receptor for SLIT1 and SLIT2 which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. May be required for lung development.<ref>PMID:10102268</ref> | + | [https://www.uniprot.org/uniprot/ROBO1_HUMAN ROBO1_HUMAN] Receptor for SLIT1 and SLIT2 which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. May be required for lung development.<ref>PMID:10102268</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Inoue, T]] | + | [[Category: Inoue T]] |
| - | [[Category: Kado, Y]] | + | [[Category: Kado Y]] |
| - | [[Category: Mizohata, E]] | + | [[Category: Mizohata E]] |
| - | [[Category: Nakayama, T]] | + | [[Category: Nakayama T]] |
| - | [[Category: Angiogenesis]]
| + | |
| - | [[Category: Antibody drug]]
| + | |
| - | [[Category: Hepatocellular carcinoma antigen]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Single chain fv fragment]]
| + | |
| Structural highlights
Function
ROBO1_HUMAN Receptor for SLIT1 and SLIT2 which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. May be required for lung development.[1]
Publication Abstract from PubMed
To investigate favorable single amino acid substitutions that improve antigen-antibody interactions, alanine (Ala) mutagenesis scanning of the interfacial residues of a cancer-targeted antibody, B5209B, was performed based on X-ray crystallography analysis. Two substitutions were shown to significantly enhance the binding affinity for the antigen, by up to 30-fold. One substitution improved the affinity by a gain of binding enthalpy, whereas the other substitution improved the affinity by a gain of binding entropy. Molecular dynamics simulations showed that the enthalpic improvement could be attributed to the stabilization of distant salt bridges located at the periphery of the antigen-antibody interface. The entropic improvement was due to the release of water molecules that were stably trapped in the antigen-antibody interface of the wild-type antibody. Importantly, these effects of the Ala substitutions were caused by subtle adjustments of the binding interface. These results will be helpful to design high-affinity antibodies with avoiding entropy-enthalpy compensation.
Affinity Improvement of a Cancer-Targeted Antibody through Alanine-Induced Adjustment of Antigen-Antibody Interface.,Yamashita T, Mizohata E, Nagatoishi S, Watanabe T, Nakakido M, Iwanari H, Mochizuki Y, Nakayama T, Kado Y, Yokota Y, Matsumura H, Kawamura T, Kodama T, Hamakubo T, Inoue T, Fujitani H, Tsumoto K Structure. 2018 Nov 20. pii: S0969-2126(18)30421-0. doi:, 10.1016/j.str.2018.11.002. PMID:30595454[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell. 1999 Mar 19;96(6):795-806. PMID:10102268
- ↑ Yamashita T, Mizohata E, Nagatoishi S, Watanabe T, Nakakido M, Iwanari H, Mochizuki Y, Nakayama T, Kado Y, Yokota Y, Matsumura H, Kawamura T, Kodama T, Hamakubo T, Inoue T, Fujitani H, Tsumoto K. Affinity Improvement of a Cancer-Targeted Antibody through Alanine-Induced Adjustment of Antigen-Antibody Interface. Structure. 2018 Nov 20. pii: S0969-2126(18)30421-0. doi:, 10.1016/j.str.2018.11.002. PMID:30595454 doi:http://dx.doi.org/10.1016/j.str.2018.11.002
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