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| | <StructureSection load='1t3f' size='340' side='right'caption='[[1t3f]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1t3f' size='340' side='right'caption='[[1t3f]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t3f]] 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=1T3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T3F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t3f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T3F FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1t04|1t04]], [[1b2w|1b2w]], [[1b4j|1b4j]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=1t3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t3f OCA], [http://pdbe.org/1t3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t3f RCSB], [http://www.ebi.ac.uk/pdbsum/1t3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t3f 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=1t3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t3f OCA], [https://pdbe.org/1t3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t3f RCSB], [https://www.ebi.ac.uk/pdbsum/1t3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t3f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bourne, P C]] | + | [[Category: Bourne PC]] |
| - | [[Category: Cloud, G]] | + | [[Category: Cloud G]] |
| - | [[Category: Edmundson, A B]] | + | [[Category: Edmundson AB]] |
| - | [[Category: Landolfi, N F]] | + | [[Category: Landolfi NF]] |
| - | [[Category: Terzyan, S S]] | + | [[Category: Terzyan SS]] |
| - | [[Category: Vasquez, M]] | + | [[Category: Vasquez M]] |
| - | [[Category: Antibody engineering]]
| + | |
| - | [[Category: Fab]]
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| - | [[Category: Gamma-interferon]]
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| - | [[Category: Humanized and chimeric antibody]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
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
Three-dimensional structures were determined for two crystal forms (orthorhombic P2(1)2(1)2(1) and monoclinic C2) of the Fab from the humanized version of a murine monoclonal antibody (AF2) that possesses binding and potent neutralizing activity against human interferon gamma (IFN-gamma). This humanized antibody (HuZAF; USAN name fontolizumab) is currently in phase II clinical trials for the treatment of Crohn's disease. HuZAF exhibits binding and IFN-gamma neutralizing capacities that closely approximate those of the original antibody. It is shown that HuZAF, whose VH domain was designed using a best-sequence-fit approach, is closer structurally to its mouse precursor than is a version whose VH was constructed using a human sequence with lower homology to the original mouse sequence. This work thus offers direct structural evidence in support of the best-sequence-fit approach and adds to previous results of biological and biochemical evaluations of distinctly engineered antibodies that also favored the use of a best-sequence-fit strategy. A second crystal type appeared during attempts to crystallize the Fab-IFN-gamma complex. The antibody-antigen complex that existed in solution dissociated in the crystallization mixture. A conformationally altered but unliganded HuZAF protein crystallized in a different space group (C2), with two Fab molecules in the asymmetric unit. In this crystal lattice, no space was available for accommodating the IFN-gamma antigen. Thus, there are currently three slightly different structures of the HuZAF Fab.
Three-dimensional structures of a humanized anti-IFN-gamma Fab (HuZAF) in two crystal forms.,Bourne PC, Terzyan SS, Cloud G, Landolfi NF, Vasquez M, Edmundson AB Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1761-9. Epub 2004, Sep 23. PMID:15388922[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bourne PC, Terzyan SS, Cloud G, Landolfi NF, Vasquez M, Edmundson AB. Three-dimensional structures of a humanized anti-IFN-gamma Fab (HuZAF) in two crystal forms. Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1761-9. Epub 2004, Sep 23. PMID:15388922 doi:10.1107/S0907444904018670
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