6a77

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the fifth immunoglobulin domain (Ig5) of human Robo1 in complex with the Fab fragment of murine monoclonal antibody B5209B

Structural highlights

6a77 is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6a77"

@@ Line 3: / Line 3: @@
 <StructureSection load='6a77' size='340' side='right'caption='[[6a77]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6a77]] is a 3 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=6A77 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A77 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6a77]] is a 3 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=6A77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A77 FirstGlance]. <br>
-</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>
+</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>
-<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=6a77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a77 OCA], [http://pdbe.org/6a77 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a77 RCSB], [http://www.ebi.ac.uk/pdbsum/6a77 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a77 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=6a77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a77 OCA], [https://pdbe.org/6a77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a77 RCSB], [https://www.ebi.ac.uk/pdbsum/6a77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a77 ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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]]

6a77

From Proteopedia

Current revision

Crystal structure of the fifth immunoglobulin domain (Ig5) of human Robo1 in complex with the Fab fragment of murine monoclonal antibody B5209B

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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