3iu3

Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomainCrystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomain

Structural highlights 3iu3 is a 9 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Gene: IL-2Ra (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [IL2RA_HUMAN] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:601942]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Function [IL2RA_HUMAN] Receptor for interleukin-2. 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 IL-2 signaling plays a central role in the initiation and activation of immune responses. Correspondingly, blockage of this pathway leads to inhibition of the immune system and would provide some therapeutic benefits. Basiliximab (Simulect), a therapeutic mAb drug with specificity against IL-2R alpha of T cells, was approved by U.S. Food and Drug Administration in 1998. It has been proven to be effective in the suppression of the IL-2 pathway and hence has been widely used to prevent allograft rejection in organ transplantation, especially in kidney transplants. In this study, we report the crystal structure of the basiliximab Fab in complex with the ectodomain of IL-2R alpha at 2.9 A resolution. In the complex structure, the Fab interacts with IL-2R alpha with extensive hydrophobic and hydrophilic interactions, accounting for a high binding affinity of 0.14 nM. The Ag binding site of basiliximab consists of all six CDR loops that form a large binding interface with a central shallow hydrophobic groove surrounded by four hydrophilic patches. The discontinuous epitope is composed of several segments from the D1 domain and a minor segment from the D2 domain that overlap with most of the regions responsible for the interactions with IL-2. Thus, basiliximab binding can completely block the interactions of IL-2 with IL-2R alpha and hence inhibit the activation of the IL-2 signal pathway. The structural results also provide important implications for the development of improved and new IL-2R alpha-targeted mAb drugs. Structural basis for the blockage of IL-2 signaling by therapeutic antibody basiliximab.,Du J, Yang H, Zhang D, Wang J, Guo H, Peng B, Guo Y, Ding J J Immunol. 2010 Feb 1;184(3):1361-8. Epub 2009 Dec 23. PMID:20032294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin receptor 3D structures of monoclonal antibody

spinqualitylabelsall models 3iu3, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image