Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yachnin BJ, Azouz LR, White RE 3rd, Minetti CASA, Remeta DP, Tan VM, Drake JM, Khare SD. Massively parallel, computationally guided design of a proenzyme. Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2116097119. doi:, 10.1073/pnas.2116097119. Epub 2022 Apr 4. PMID:35377786 doi:http://dx.doi.org/10.1073/pnas.2116097119