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The crystal structure of the IPNS\u2010cyclobutanone complex reveals an active site environment similar to that seen in the enzyme\u2013product complex generated by turnover of the natural substrate within the crystalline protein. The IPNS\u2013cyclobutanone structure demonstrates that the product analogue is tethered to the protein by hydrogen bonding and salt bridge interactions with its carboxylate groups, as seen previously for the natural substrate and product. 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