Structural highlights
Function
[DFPA_LOLVU] Biological function and substrate unknown. However, it is capable of acting on phosphorus anhydride bonds (such as phosphorus-halide and phosphorus-cyanide) in organophosphorus compounds (including nerve gases).[1]
Publication Abstract from PubMed
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.
Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.,Eiben CB, Siegel JB, Bale JB, Cooper S, Khatib F, Shen BW, Players F, Stoddard BL, Popovic Z, Baker D Nat Biotechnol. 2012 Jan 22;30(2):190-2. doi: 10.1038/nbt.2109. PMID:22267011[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Katsemi V, Lucke C, Koepke J, Lohr F, Maurer S, Fritzsch G, Ruterjans H. Mutational and structural studies of the diisopropylfluorophosphatase from Loligo vulgaris shed new light on the catalytic mechanism of the enzyme. Biochemistry. 2005 Jun 28;44(25):9022-33. PMID:15966726 doi:10.1021/bi0500675
- ↑ Eiben CB, Siegel JB, Bale JB, Cooper S, Khatib F, Shen BW, Players F, Stoddard BL, Popovic Z, Baker D. Increased Diels-Alderase activity through backbone remodeling guided by Foldit players. Nat Biotechnol. 2012 Jan 22;30(2):190-2. doi: 10.1038/nbt.2109. PMID:22267011 doi:http://dx.doi.org/10.1038/nbt.2109
