3U0S
Crystal Structure of an Enzyme Redesigned Through Multiplayer Online Gaming: CE6
Summary for 3U0S
| Entry DOI | 10.2210/pdb3u0s/pdb |
| Related | 1E1A 3I1C |
| Descriptor | Diisopropyl-fluorophosphatase, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | protein engineering, computer-aided design, computationally-directed design, multiplayer online gaming, crowdsourcing, foldit, diels-alder, enzyme design, active site redesign, substrate specificity, beta-propeller, helix-loop-helix, loop remodel, hydrolase, de novo protein |
| Biological source | Loligo vulgaris (Common European squid) |
| Total number of polymer chains | 2 |
| Total formula weight | 76536.43 |
| Authors | Bale, J.B.,Shen, B.W.,Stoddard, B.L. (deposition date: 2011-09-29, release date: 2012-02-01, Last modification date: 2024-02-28) |
| Primary citation | Eiben, C.B.,Siegel, J.B.,Bale, J.B.,Cooper, S.,Khatib, F.,Shen, B.W.,Players, F.,Stoddard, B.L.,Popovic, Z.,Baker, D. Increased Diels-Alderase activity through backbone remodeling guided by Foldit players. Nat.Biotechnol., 30:190-192, 2012 Cited by PubMed Abstract: Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems. PubMed: 22267011DOI: 10.1038/nbt.2109 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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