1t04: Difference between revisions
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'''Three dimensional structure of a humanized anti-IFN-Gamma Fab in C2 space group''' | '''Three dimensional structure of a humanized anti-IFN-Gamma Fab in C2 space group''' | ||
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==About this Structure== | ==About this Structure== | ||
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T04 OCA]. | |||
==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/15388922 15388922] | 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] | ||
[[Category: Bourne, P C.]] | [[Category: Bourne, P C.]] | ||
[[Category: Cloud, G.]] | [[Category: Cloud, G.]] | ||
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[[Category: Terzyan, S S.]] | [[Category: Terzyan, S S.]] | ||
[[Category: Vasquez, M.]] | [[Category: Vasquez, M.]] | ||
[[Category: | [[Category: Antibody engineering]] | ||
[[Category: | [[Category: Fab]] | ||
[[Category: | [[Category: Gamma-interferon]] | ||
[[Category: | [[Category: Humanized and chimeric antibody]] | ||
[[Category: | [[Category: Immune system]] | ||
[[Category: | [[Category: Three-dimensional structure]] | ||
[[Category: | [[Category: X-ray structure]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:20:15 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 06:20, 3 May 2008
Three dimensional structure of a humanized anti-IFN-Gamma Fab in C2 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
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 Sat May 3 09:20:15 2008
