{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T06:55:15Z","timestamp":1775372115533,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistrySelect"],"published-print":{"date-parts":[[2018,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) is the bacteria that currently claims the most number of human lives each year. The final step of peptidoglycan synthesis involves the generation of 4\u21923 and 3\u21923 transpeptide crosslinks catalyzed by D,D\u2010transpeptidase and L,D\u2010transpeptidase (Ldt) enzymes, respectively. Unlike in most other bacteria, for\n                    <jats:italic>Mtb<\/jats:italic>\n                    , the majority of the cross\u2010links are generated by L,D\u2010transpeptidases. Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    knock\u2010out strains of\n                    <jats:italic>Mtb<\/jats:italic>\n                    displayed aberrant growth, and are susceptibility to crystal violet, osmotic shock, and selected carbapenem antibiotics. Here, we used molecular dynamics (MD) and Quantum Mechanical (QM) simulations to probe the molecular interactions of Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    with carbapenems. Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    complexes with three carbapenems, ertapenem (ERT), imipenem (IMI) and meropenem (MERO) were simulated. The binding free energies of these complexes were calculated from the MD trajectories using the MM\/GBSA approach, the theoretical results revealed higher \u25b5\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>bind<\/jats:sub>\n                    for ERT\u2014Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    and IMI\u2014Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    than MERO\u2014Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    . To further understand the catalytic reaction mechanism of Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    with the selected carbapenems, the possible reaction pathway was investigated. The high free energies of activation (\u25b5\n                    <jats:italic>G<\/jats:italic>\n                    ) for imipenem and meropenem, explain the reason behind inefficient binding of these carbapenems to Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    . These results provide a better understanding of how the antibacterial agents function and will potentially contribute to the discovery of more potent Ldt\n                    <jats:sub>Mt5<\/jats:sub>\n                    inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/slct.201803184","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T16:08:24Z","timestamp":1545408504000},"page":"13603-13612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    L,D\u2010Transpeptidase 5\u2009by Carbapenems: MD and QM\/MM Mechanistic Studies"],"prefix":"10.1002","volume":"3","author":[{"given":"Gideon F.","family":"Tolufashe","sequence":"first","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Amit K.","family":"Halder","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Collins U.","family":"Ibeji","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Monsurat M.","family":"Lawal","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Thandokuhle","family":"Ntombela","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Thavendran","family":"Govender","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"given":"Glenn E. M.","family":"Maguire","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"},{"name":"School of Chemistry and Physics University of KwaZulu-Natal  4001 Durban South Africa"}]},{"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases School of Medicine Johns Hopkins University  Baltimore MD 21205 USA"}]},{"given":"Hendrik G.","family":"Kruger","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0852-9756","authenticated-orcid":false,"given":"Bahareh","family":"Honarparvar","sequence":"additional","affiliation":[{"name":"Catalysis and Peptide Research Unit School of Health Sciences University of KwaZulu-Natal  Durban 4001 South Africa"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.7.677"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71877-8"},{"key":"e_1_2_6_3_1","unstructured":"N.\u2005I.\u2005O. 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