6s6e | pdb_00006s6e

Crystal structure of the engineered ancestor of haloalkane dehalogenases and Renilla luciferase (AncHLD-RLuc I161_F162PinsL)

spinqualitylabelsall models 6s6e, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6s6e is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.001Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein Anc(HLD-RLuc) which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of Anc(HLD-RLuc) challenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment of Renilla luciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins. Engineering the protein dynamics of an ancestral luciferase.,Schenkmayerova A, Pinto GP, Toul M, Marek M, Hernychova L, Planas-Iglesias J, Daniel Liskova V, Pluskal D, Vasina M, Emond S, Dorr M, Chaloupkova R, Bednar D, Prokop Z, Hollfelder F, Bornscheuer UT, Damborsky J Nat Commun. 2021 Jun 14;12(1):3616. doi: 10.1038/s41467-021-23450-z. PMID:34127663 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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