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1t3f
From Proteopedia
(New page: 200px<br /> <applet load="1t3f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t3f, resolution 2.00Å" /> '''THREE DIMENSIONAL S...) |
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| - | [[Image:1t3f.gif|left|200px]]<br /> | + | [[Image:1t3f.gif|left|200px]]<br /><applet load="1t3f" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t3f" size=" | + | |
caption="1t3f, resolution 2.00Å" /> | caption="1t3f, resolution 2.00Å" /> | ||
'''THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP'''<br /> | '''THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Three-dimensional structures were determined for two crystal forms | + | 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== | ==About this Structure== | ||
| - | 1T3F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1T3F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://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]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 13: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bourne, P | + | [[Category: Bourne, P C.]] |
[[Category: Cloud, G.]] | [[Category: Cloud, G.]] | ||
| - | [[Category: Edmundson, A | + | [[Category: Edmundson, A B.]] |
| - | [[Category: Landolfi, N | + | [[Category: Landolfi, N F.]] |
| - | [[Category: Terzyan, S | + | [[Category: Terzyan, S S.]] |
[[Category: Vasquez, M.]] | [[Category: Vasquez, M.]] | ||
[[Category: antibody engineering]] | [[Category: antibody engineering]] | ||
| Line 27: | Line 26: | ||
[[Category: x-ray structure]] | [[Category: x-ray structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:24 2008'' |
Revision as of 13:09, 21 February 2008
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THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP
Overview
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
1T3F is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 15:09:24 2008
