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==THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP== | |||
<StructureSection load='1t3f' size='340' side='right'caption='[[1t3f]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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'>[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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t3/1t3f_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<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/main_output.php?pdb_ID=1t3f ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:15388922</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1t3f" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bourne | [[Category: Large Structures]] | ||
[[Category: Cloud | [[Category: Bourne PC]] | ||
[[Category: Edmundson | [[Category: Cloud G]] | ||
[[Category: Landolfi | [[Category: Edmundson AB]] | ||
[[Category: Terzyan | [[Category: Landolfi NF]] | ||
[[Category: Vasquez | [[Category: Terzyan SS]] | ||
[[Category: Vasquez M]] | |||
Latest revision as of 03:30, 21 November 2024
THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUPTHREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP
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 PubMedThree-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 AlsoReferences
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