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1t3f

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{{STRUCTURE_1t3f| PDB=1t3f | SCENE= }}
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'''THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP'''
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===THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15388922}}
==About this Structure==
==About this Structure==
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[[Category: Immune system]]
[[Category: Immune system]]
[[Category: X-ray structure]]
[[Category: X-ray structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:15:06 2008''

Revision as of 16:15, 27 July 2008

Image:1t3f.png

Template:STRUCTURE 1t3f

THREE DIMENSIONAL STRUCTURE OF A HUMANIZED ANTI-IFN-GAMMA FAB (HuZAF) IN P21 21 21 SPACE GROUP

Template:ABSTRACT PUBMED 15388922

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

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