4a2r

Structure of the engineered retro-aldolase RA95.5-5

spinqualitylabelsall models 4a2r, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4a2r is a 1 chain structure with sequence from Saccharolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.302Å Ligands: 3NK Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRPC_SACS2 Publication Abstract from PubMed Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that pronounced molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400-fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate-binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. Evolution of a designed retro-aldolase leads to complete active site remodeling.,Giger L, Caner S, Obexer R, Kast P, Baker D, Ban N, Hilvert D Nat Chem Biol. 2013 Jun 9. doi: 10.1038/nchembio.1276. PMID:23748672 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures IGPS 3D structures

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