3eo1

From Proteopedia

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

PDB ID 3eo1

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Structural highlights

3eo1 is a 12 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGHG4_HUMAN

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG. A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914 doi:0807200106