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N-succinyl-<jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-diaminopimelic acid desuccinylase (DapE) is a key enzyme in the succinylase pathway for the biosynthesis of meso-diaminopimelic acid (meso-DAP) and <jats:bold>L<\/jats:bold>-lysine. DapE is a zinc containing metallohydrolase which hydrolyses N-succinyl <jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold> diaminopimelic acid (<jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-NSDAP) to <jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-diaminopimelic acid (<jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-DAP) and succinate. <jats:italic>M. tuberculosis<\/jats:italic> DapE (MtDapE) was cloned, over-expressed and purified as an N-terminal hexahistidine ((His)<jats:sub>6<\/jats:sub>) tagged fusion containing one zinc ion per DapE monomer. We redesigned the DAP synthetic pathway to generate <jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-NSDAP and other <jats:bold>L<\/jats:bold>,<jats:bold>L<\/jats:bold>-NSDAP derivatives and have characterised MtDapE with these substrates. In contrast to its other Gram negative homologues, the MtDapE was insensitive to inhibition by <jats:bold>L<\/jats:bold>-captopril which we show is consistent with novel mycobacterial alterations in the binding site of this drug.<\/jats:p>","DOI":"10.1038\/srep23191","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T11:08:54Z","timestamp":1458040134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Reconstruction of diaminopimelic acid biosynthesis allows characterisation of Mycobacterium tuberculosis N-succinyl-L,L-diaminopimelic acid desuccinylase"],"prefix":"10.1038","volume":"6","author":[{"given":"Veeraraghavan","family":"Usha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Roper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Dowson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guennadi","family":"Kozlov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Gehring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan T.","family":"Imam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Blindauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurdyal S.","family":"Besra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"BFsrep23191_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(12)61812-1","volume":"381","author":"C Dye","year":"2013","unstructured":"Dye, C. et al. 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