3eo1 | pdb_00003eo1

Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3

spinqualitylabelsall models 3eo1, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3eo1 is a 12 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. Related: 3eo0 Gene: TGFB3 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [TGFB3_HUMAN] Defects in TGFB3 are a cause of familial arrhythmogenic right ventricular dysplasia type 1 (ARVD1) [MIM:107970]; also known as arrhythmogenic right ventricular cardiomyopathy 1 (ARVC1). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall. Function [TGFB3_HUMAN] Involved in embryogenesis and cell differentiation. 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 TGF-beta isoforms are key modulators of a broad range of biological pathways and increasingly are exploited as therapeutic targets. Here, we describe the crystal structures of a pan-TGF-beta neutralizing antibody, GC-1008, alone and in complex with TGF-beta3. The antibody is currently in clinical evaluation for idiopathic pulmonary fibrosis, melanoma, and renal cell cancer. GC-1008 recognizes an asymmetric binding interface across the TGF-beta homodimer with high affinity. Whereas both cognate receptors, TGF-beta-receptor types I and II, are required to recognize all 3 TGF-beta isoforms, GC-1008 has been engineered to bind with high affinity to TGF-beta1, 2, and 3 via a single interaction surface. Comparison with existing structures and models of TGF-beta interaction with its receptors suggests that the antibody binds to a similar epitope to the 2 receptors together and is therefore a structurally different but functionally identical mimic of the binding mode of both receptors. A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.,Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody

Proteopedia Page Contributors and Editors (what is this?)

OCA