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| {{STRUCTURE_1t3f| PDB=1t3f | SCENE= }} | | {{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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15388922}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15388922 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15388922}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Immune system]] | | [[Category: Immune system]] |
| [[Category: X-ray structure]] | | [[Category: X-ray structure]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:28:20 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:15:06 2008'' |