3eob | pdb_00003eob

Crystal structure the Fab fragment of Efalizumab in complex with LFA-1 I domain, Form II

spinqualitylabelsall models 3eob, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3eob is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Related: 3eo9, 3eoa Gene: IGG1 (HUMAN), LFA-1 I domain (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ITAL_HUMAN] Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha(L) I domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases. Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance.,Li S, Wang H, Peng B, Zhang M, Zhang D, Hou S, Guo Y, Ding J Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4349-54. Epub 2009 Mar 3. PMID:19258452 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures Monoclonal Antibodies 3D structures

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