4ou1 | pdb_00004ou1

Crystal structure of a computationally designed retro-aldolase covalently bound to folding probe 1 [(6-methoxynaphthalen-2-yl)(oxiran-2-yl)methanol]

spinqualitylabelsall models 4ou1, resolution 1.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ou1 is a 1 chain structure with sequence from Saccharolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.25Å Ligands: 2V7, BEZ, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPC_SACS2 Publication Abstract from PubMed Although much is known about protein folding in buffers, it remains unclear how the cellular protein homeostasis network functions as a system to partition client proteins between folded and functional, soluble and misfolded, and aggregated conformations. Herein, we develop small molecule folding probes that specifically react with the folded and functional fraction of the protein of interest, enabling fluorescence-based quantification of this fraction in cell lysate at a time point of interest. Importantly, these probes minimally perturb a protein's folding equilibria within cells during and after cell lysis, because sufficient cellular chaperone/chaperonin holdase activity is created by rapid ATP depletion during cell lysis. The folding probe strategy and the faithful quantification of a particular protein's functional fraction are exemplified with retroaldolase, a de novo designed enzyme, and transthyretin, a nonenzyme protein. Our findings challenge the often invoked assumption that the soluble fraction of a client protein is fully folded in the cell. Moreover, our results reveal that the partitioning of destabilized retroaldolase and transthyretin mutants between the aforementioned conformational states is strongly influenced by cytosolic proteostasis network perturbations. Overall, our results suggest that applying a chemical folding probe strategy to other client proteins offers opportunities to reveal how the proteostasis network functions as a system to regulate the folding and function of individual client proteins in vivo. Small molecule probes to quantify the functional fraction of a specific protein in a cell with minimal folding equilibrium shifts.,Liu Y, Tan YL, Zhang X, Bhabha G, Ekiert DC, Genereux JC, Cho Y, Kipnis Y, Bjelic S, Baker D, Kelly JW Proc Natl Acad Sci U S A. 2014 Mar 3. PMID:24591605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA