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1t3f
From Proteopedia
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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 Sun Nov 18 09:42:46 2007
