7m6u

Crystal structure of a circular permutation and computationally designed pro-enzyme of carboxypeptidase G2

spinqualitylabelsall models 7m6u, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7m6u is a 4 chain structure with sequence from Pseudomonas sp. RS-16 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CBPG_PSES6 Catalyzes the hydrolysis of reduced and non-reduced folates to pteroates and L-glutamate. This enzyme has a broad specificity. Publication Abstract from PubMed SignificanceProteins have shown promise as therapeutics and diagnostics, but their effectiveness is limited by our inability to spatially target their activity. To overcome this limitation, we developed a computationally guided method to design inactive proenzymes or zymogens, which are activated through cleavage by a protease. Since proteases are differentially expressed in various tissues and disease states, including cancer, these proenzymes could be targeted to the desired microenvironment. We tested our method on the therapeutically relevant protein carboxypeptidase G2 (CPG2). We designed Pro-CPG2s that are inhibited by 80 to 98% and are partially to fully reactivatable following protease treatment. The developed methodology, with further refinements, could pave the way for routinely designing protease-activated protein-based therapeutics and diagnostics that act in a spatially controlled manner. Massively parallel, computationally guided design of a proenzyme.,Yachnin BJ, Azouz LR, White RE 3rd, Minetti CASA, Remeta DP, Tan VM, Drake JM, Khare SD Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2116097119. doi:, 10.1073/pnas.2116097119. Epub 2022 Apr 4. PMID:35377786 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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