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BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE\u2010metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant\u2010state\u2010based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a &gt;400\u2010fold improved catalytic efficiency against BZE compared with wild\u2010type (WT) CocE. In vivo, a single dose of BZEase2 (1\u2005mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined.\n                  <\/jats:p>","DOI":"10.1002\/anie.202108559","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T06:31:16Z","timestamp":1628145076000},"page":"21959-21965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-3203","authenticated-orcid":false,"given":"Xiabin","family":"Chen","sequence":"first","affiliation":[{"name":"College of Pharmacy School of Medicine Hangzhou Normal University  Hangzhou Zhejiang 311121 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Pharmacy School of Medicine Hangzhou Normal University  Hangzhou 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