5lky

X-ray crystal structure of N-acetylneuraminic acid lyase in complex with pyruvate, with the phenylalanine at position 190 replaced with the non-canonical amino acid dihydroxypropylcysteine.

spinqualitylabelsall models 5lky, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lky is a 4 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: KPI, P9S, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NANA_STAA8 Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate (By similarity). Publication Abstract from PubMed Natural enzymes are constructed from the 20 proteogenic amino acids, which may then require posttranslational modification or the recruitment of coenzymes or metal ions to achieve catalytic function. Here, we demonstrate that expansion of the alphabet of amino acids can also enable the properties of enzymes to be extended. A chemical mutagenesis strategy allowed a wide range of noncanonical amino acids to be systematically incorporated throughout an active site to alter enzymic substrate specificity. Specifically, 13 different noncanonical side chains were incorporated at 12 different positions within the active site of N-acetylneuraminic acid lyase (NAL), and the resulting chemically modified enzymes were screened for activity with a range of aldehyde substrates. A modified enzyme containing a 2,3-dihydroxypropyl cysteine at position 190 was identified that had significantly increased activity for the aldol reaction of erythrose with pyruvate compared with the wild-type enzyme. Kinetic investigation of a saturation library of the canonical amino acids at the same position showed that this increased activity was not achievable with any of the 20 proteogenic amino acids. Structural and modeling studies revealed that the unique shape and functionality of the noncanonical side chain enabled the active site to be remodeled to enable more efficient stabilization of the transition state of the reaction. The ability to exploit an expanded amino acid alphabet can thus heighten the ambitions of protein engineers wishing to develop enzymes with new catalytic properties. Extending enzyme molecular recognition with an expanded amino acid alphabet.,Windle CL, Simmons KJ, Ault JR, Trinh CH, Nelson A, Pearson AR, Berry A Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2610-2615. doi:, 10.1073/pnas.1616816114. Epub 2017 Feb 14. PMID:28196894 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also N-acetylneuraminate lyase 3D structures

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