7ud6 | pdb_00007ud6

Designed Enzyme SH3-588 (Catechol O-methyltransferase catalytic domain and Src homology 3 binding domain fusion)

spinqualitylabelsall models 7ud6, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ud6 is a 1 chain structure with sequence from Homo sapiens and Rattus norvegicus. 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: K, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E5RFS5_HUMAN COMT_RAT Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. Publication Abstract from PubMed 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. Designer installation of a substrate recruitment domain to tailor enzyme specificity.,Park R, Ongpipattanakul C, Nair SK, Bowers AA, Kuhlman B Nat Chem Biol. 2022 Dec 12. doi: 10.1038/s41589-022-01206-0. PMID:36509904 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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