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3hmw

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Revision as of 14:19, 27 April 2017

Crystal structure of ustekinumab FAB

Structural highlights

3hmw is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Interleukin (IL)-12 and IL-23 are heterodimeric proinflammatory cytokines that share a common p40 subunit, paired with p35 and p19 subunits, respectively. They represent an attractive class of therapeutic targets for the treatment of psoriasis and other immune-mediated diseases. Ustekinumab is a fully human monoclonal antibody (mAb) that binds specifically to IL-12/IL-23p40 and neutralizes human IL-12 and IL-23 bioactivity. The crystal structure of ustekinumab Fab (antigen binding fragment of mAb), in complex with human IL-12, has been determined by X-ray crystallography at 3.0 A resolution. Ustekinumab Fab binds the D1 domain of the p40 subunit in a 1:1 ratio in the crystal, consistent with a 2 cytokines:1 mAb stoichiometry, as measured by isothermal titration calorimetry. The structure indicates that ustekinumab binds to the same epitope on p40 in both IL-12 and IL-23 with identical interactions. Mutational analyses confirm that several residues identified in the IL-12/IL-23p40 epitope provide important molecular binding interactions with ustekinumab. The electrostatic complementarity between the mAb antigen binding site and the p40 D1 domain epitope appears to play a key role in antibody/antigen recognition specificity. Interestingly, this structure also reveals significant structural differences in the p35 subunit and p35/p40 interface, compared with the published crystal structure of human IL-12, suggesting unusual and potentially functionally relevant structural flexibility of p35, as well as p40/p35 recognition. Collectively, these data describe unique observations about IL-12p35 and ustekinumab interactions with p40 that account for its dual binding and neutralization of IL-12 and IL-23.

Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab.,Luo J, Wu SJ, Lacy ER, Orlovsky Y, Baker A, Teplyakov A, Obmolova G, Heavner GA, Richter HT, Benson J J Mol Biol. 2010 Oct 8;402(5):797-812. Epub 2010 Aug 4. PMID:20691190^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Luo J, Wu SJ, Lacy ER, Orlovsky Y, Baker A, Teplyakov A, Obmolova G, Heavner GA, Richter HT, Benson J. Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab. J Mol Biol. 2010 Oct 8;402(5):797-812. Epub 2010 Aug 4. PMID:20691190 doi:10.1016/j.jmb.2010.07.046

1 Structural highlights
2 Evolutionary Conservation
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/3hmw"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ustekinumab FAB==
 <StructureSection load='3hmw' size='340' side='right' caption='[[3hmw]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3hmw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HMW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HMW FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</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=3hmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hmw RCSB], [http://www.ebi.ac.uk/pdbsum/3hmw PDBsum]</span></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=3hmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hmw OCA], [http://pdbe.org/3hmw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hmw RCSB], [http://www.ebi.ac.uk/pdbsum/3hmw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hmw ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 14: / Line 15: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hmw ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 24: / Line 25: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3hmw" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
 == References ==
 <references/>

3hmw

From Proteopedia

Revision as of 14:19, 27 April 2017

Crystal structure of ustekinumab FAB

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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