7UD6
Designed Enzyme SH3-588 (Catechol O-methyltransferase catalytic domain and Src homology 3 binding domain fusion)
Summary for 7UD6
| Entry DOI | 10.2210/pdb7ud6/pdb |
| Descriptor | Tyrosine-protein kinase Fyn,Catechol O-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, POTASSIUM ION, ... (4 entities in total) |
| Functional Keywords | designed enzyme, comt, sh3, fusion protein, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 33057.52 |
| Authors | Ongpipattanakul, C.,Nair, S.K. (deposition date: 2022-03-18, release date: 2023-01-11, Last modification date: 2023-10-25) |
| Primary citation | Park, R.,Ongpipattanakul, C.,Nair, S.K.,Bowers, A.A.,Kuhlman, B. Designer installation of a substrate recruitment domain to tailor enzyme specificity. Nat.Chem.Biol., 19:460-467, 2023 Cited by PubMed Abstract: Promiscuous enzymes that modify peptides and proteins are powerful tools for labeling biomolecules; however, directing these modifications to desired substrates can be challenging. Here, we use computational interface design to install a substrate recognition domain adjacent to the active site of a promiscuous enzyme, catechol O-methyltransferase. This design approach effectively decouples substrate recognition from the site of catalysis and promotes modification of peptides recognized by the recruitment domain. We determined the crystal structure of this novel multidomain enzyme, SH3-588, which shows that it closely matches our design. SH3-588 methylates directed peptides with catalytic efficiencies exceeding the wild-type enzyme by over 1,000-fold, whereas peptides lacking the directing recognition sequence do not display enhanced efficiencies. In competition experiments, the designer enzyme preferentially modifies directed substrates over undirected substrates, suggesting that we can use designed recruitment domains to direct post-translational modifications to specific sequence motifs on target proteins in complex multisubstrate environments. PubMed: 36509904DOI: 10.1038/s41589-022-01206-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.59 Å) |
Structure validation
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