6sq8

Structure of amide bond synthetase McbA from Marinactinospora thermotolerans

spinqualitylabelsall models 6sq8, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sq8 is a 5 chain structure with sequence from Marinactinospora thermotolerans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: AMP, EQ2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function R4R1U5_9ACTN Publication Abstract from PubMed The biocatalytic synthesis of amides from carboxylic acids and primary amines in aqueous media can be achieved using the ATP-dependent amide bond synthetase McbA, via an adenylate intermediate, using only 1.5 equiv of the amine nucleophile. Following earlier studies that characterized the broad carboxylic acid specificity of McbA, we now show that, in addition to the natural amine substrate 2-phenylethylamine, a range of simple aliphatic amines, including methylamine, butylamine, and hexylamine, and propargylamine are coupled efficiently to the native carboxylic acid substrate 1-acetyl-9H-beta-carboline-3-carboxylic acid by the enzyme, to give amide products with up to >99% conversion. The structure of wild-type McbA in its amidation conformation, coupled with modeling and mutational studies, reveal an amine access tunnel and a possible role for residue D201 in amine activation. Amide couplings were slower with anilines and alicyclic secondary amines such as pyrrolidine and piperidine. The broader substrate specificity of McbA was exploited in the synthesis of the monoamine oxidase A inhibitor moclobemide, through the reaction of 4-chlorobenzoic acid with 1.5 equiv of 4-(2-aminoethyl)morpholine, and utilizing polyphosphate kinases SmPPK and AjPPK in the presence of polyphosphoric acid and 0.1 equiv of ATP, required for recycling of the cofactor. Biocatalytic Synthesis of Moclobemide Using the Amide Bond Synthetase McbA Coupled with an ATP Recycling System.,Petchey MR, Rowlinson B, Lloyd RC, Fairlamb IJS, Grogan G ACS Catal. 2020 Apr 17;10(8):4659-4663. doi: 10.1021/acscatal.0c00929. Epub 2020 , Mar 30. PMID:32337091 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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