4ipx

Analyzing the visible conformational substates of the FK506 binding protein FKBP12

spinqualitylabelsall models 4ipx, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ipx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MPD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FKB1A_HUMAN Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Publication Abstract from PubMed The 1H-15N 2D NMR correlation spectrum of the widely studied FK506-binding protein FKBP12 contains previously unreported peak doublings for at least 31 residues that arise from a minor conformational state (12% of total) which exchanges with the major conformation with a time constant of 3.0 s at 43oC. The largest differences in chemical shift occur for the 80's loop that forms critical recognition interactions with many of the protein partners for the FKBP family. The residues exhibiting doubling extend into the adjacent strands of the beta sheet, across the active site to the alpha helix and into the 50's loop. Each of the seven proline residues adopts a trans peptide linkage in both the major and minor conformations, indicating that this slow transition is not the result of prolyl isomerization. Many of the residues exhibiting resonance doubling also participate in conformational linebroadening transition(s) that occur ~105-fold more rapidly, previously proposed to arise from a single global process. The 1.70 A resolution X-ray structure of the H87V variant is strikingly similar to that of FKBP12, yet this substitution quenches the slow conformational transition throughout the protein while quenching the linebroadening transition for residues near the 80's loop. Linebroadening was also decreased for the residues in the alpha-helix and 50's loop, while linebroadening in the 40's loop was unaffected. The K44V mutation selectively reduces the linebroadening in the 40's loop, verifying that at least three distinct conformational transitions underlie the linebroadening processes of FKBP12. Analyzing the visible conformational substates of the FK506-binding protein FKBP12.,Mustafi SM, Chen H, Li H, Lemaster DM, Hernandez G Biochem J. 2013 May 21. PMID:23688288 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also FKBP 3D structures

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