4kxz | pdb_00004kxz

crystal structure of tgfb2 in complex with GC2008.

spinqualitylabelsall models 4kxz, resolution 2.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kxz is a 12 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 2.83Å Ligands: MES, PE5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TGFB2_HUMAN Note=A chromosomal aberration involving TGFB2 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with HDAC9. Defects in TGFB2 are the cause of Loeys-Dietz syndrome 4 (LDS4) [MIM:614816. An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae. Function TGFB2_HUMAN TGF-beta 2 has suppressive effects on interleukin-2 dependent T-cell growth. Publication Abstract from PubMed Various important biological pathways are modulated by TGFbeta isoforms; as such they are potential targets for therapeutic intervention. Fresolimumab, also known as GC1008, is a pan-TGFbeta neutralizing antibody that has been tested clinically for several indications including an ongoing trial for focal segmental glomerulosclerosis. The structure of the antigen-binding fragment of fresolimumab (GC1008 Fab) in complex with TGFbeta3 has been reported previously, but the structural capacity of fresolimumab to accommodate tight interactions with TGFbeta1 and TGFbeta2 was insufficiently understood. We report the crystal structure of the single-chain variable fragment of fresolimumab (GC1008 scFv) in complex with target TGFbeta1 to a resolution of 3.00 A and the crystal structure of GC1008 Fab in complex with TGFbeta2 to 2.83 A. The structures provide further insight into the details of TGFbeta recognition by fresolimumab, give a clear indication of the determinants of fresolimumab pan-specificity and provide potential starting points for the development of isoform-specific antibodies using a fresolimumab scaffold. Structures of a pan-specific antagonist antibody complexed to different isoforms of TGFbeta reveal structural plasticity of antibody-antigen interactions.,Moulin A, Mathieu M, Lawrence C, Bigelow R, Levine M, Hamel C, Marquette JP, Le Parc J, Loux C, Ferrari P, Capdevila C, Dumas J, Dumas B, Rak A, Bird J, Qiu H, Pan CQ, Edmunds T, Wei RR Protein Sci. 2014 Sep 10. doi: 10.1002/pro.2548. PMID:25209176 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA