1t3f: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1t3f.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_1t3f", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1t3f|  PDB=1t3f  |  SCENE=  }}
'''THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP'''


==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]] 2.00&Aring;' 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]] 2&#8491;</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.


==Overview==
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>
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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T3F OCA].
</div>
<div class="pdbe-citations 1t3f" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/15388922 15388922]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
[[Category: Bourne, P C.]]
== References ==
[[Category: Cloud, G.]]
<references/>
[[Category: Edmundson, A B.]]
__TOC__
[[Category: Landolfi, N F.]]
</StructureSection>
[[Category: Terzyan, S S.]]
[[Category: Homo sapiens]]
[[Category: Vasquez, M.]]
[[Category: Large Structures]]
[[Category: Antibody engineering]]
[[Category: Bourne PC]]
[[Category: Fab]]
[[Category: Cloud G]]
[[Category: Gamma-interferon]]
[[Category: Edmundson AB]]
[[Category: Humanized and chimeric antibody]]
[[Category: Landolfi NF]]
[[Category: Immune system]]
[[Category: Terzyan SS]]
[[Category: X-ray structure]]
[[Category: Vasquez M]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 09:28:20 2008''
Retrieved from "https://proteopedia.org/1t3f"