4hj0 | pdb_00004hj0

Crystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolution

spinqualitylabelsall models 4hj0, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hj0 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GIPR_HUMAN This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMed Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that upon binding to its receptor (GIPr; a class B GPCR), stimulates insulin secretion by beta cells in the pancreas, There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure, to investigate GIP biology. Here we describe here the generation of an antagonizing antibody to the GIPr, using phage and ribosome display libraries. Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog and human GIP receptors with a Ki of 7 nM for the human GIPr. Gipg013 antagonises the GIP receptor and inhibits GIP induced insulin secretion in vivo. A crystal structure of Gipg013 Fab in complex with the human GIPr ECD indicates that the antibody binds through a series of hydrogen bonds from the CDRs of Gipg013 Fab to the N-terminal alpha-helix of GIPr extracellular domain (ECD) as well as to residues around its highly conserved glucagon receptor sub-family recognition fold. The antibody epitope overlaps with the GIP binding site on GIPr ECD ensuring competitive antagonism of the receptor. This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. Structural and Pharmacological Characterisation of Novel Potent and Selective Monoclonal Antibody Antagonists of Glucose-Dependent Insulinotropic Polypeptide Receptor.,Ravn P, Madhurantakam C, Kunze S, Matthews E, Priest C, O'brien S, Collinson A, Papworth M, Fritsch-Fredin M, Jermutus L, Benthem L, Gruetter M, Jackson RH J Biol Chem. 2013 May 20. PMID:23689510 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Glucose-dependent Insulinotropic Polypeptide Receptor Monoclonal Antibodies 3D structures 3D structures of human antibody

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