{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:03:04Z","timestamp":1793930584570,"version":"4.8.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T00:00:00Z","timestamp":1359504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006224","name":"Argonne National Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM094585"],"award-info":[{"award-number":["GM094585"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM094568"],"award-info":[{"award-number":["GM094568"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"publisher","award":["DE\u2010AC02\u201006CH11357"],"award-info":[{"award-number":["DE\u2010AC02\u201006CH11357"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>\n                    The specter of a return to an era in which infectious disease looms as a significant threat to human health is not just hyperbole; there are serious concerns about the widespread overuse and misuse of antibiotics contributing to increased antibiotic resistance in pathogens. The recent discovery of a new enzyme, first identified in\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    from a patient from New Delhi and denoted as NDM\u20101, represents an example of extreme promiscuity: It hydrolyzes and inactivates nearly all known \u03b2\u2010lactam\u2010based antibiotics with startling efficiency. NDM\u20101 can utilize different metal cofactors and seems to exploit an alternative mechanism based on the reaction conditions. Here we report the results of a combined experimental and theoretical study that examines the substrate, metal binding, and catalytic mechanism of the enzyme. We utilize structures obtained through X\u2010ray crystallography, biochemical assays, and numerical simulation to construct a model of the enzyme catalytic pathway. The NDM\u20101 enzyme interacts with the substrate solely through zinc, or other metals, bound in the active site, explaining the observed lack of specificity against a broad range of \u03b2\u2010lactam antibiotic agents. The zinc ions also serve to activate a water molecule that hydrolyzes the \u03b2\u2010lactam ring through a proton shuttle.\u2014Kim, Y., Cunningham, M. A.; Mire, J., Tesar, C., Sacchettini, J., Joachimiak, A. NDM\u20101, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1917\u20131927 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-224014","type":"journal-article","created":{"date-parts":[[2013,1,30]],"date-time":"2013-01-30T21:13:53Z","timestamp":1359580433000},"page":"1917-1927","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["NDM\u20101, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism"],"prefix":"10.1096","volume":"27","author":[{"given":"Youngchang","family":"Kim","sequence":"first","affiliation":[{"name":"Midwest Center for Structural Genomics Argonne National Laboratory Argonne Illinois USA"},{"name":"Structural Biology Center, Biosciences Division Argonne National Laboratory Argonne Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Physics and Geology University of Texas\u2013Pan American Edinburg Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Mire","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Tesar","sequence":"additional","affiliation":[{"name":"Midwest Center for Structural Genomics Argonne National Laboratory Argonne Illinois USA"},{"name":"Structural Biology Center, Biosciences Division Argonne National Laboratory Argonne Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Texas A&amp;M University College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Joachimiak","sequence":"additional","affiliation":[{"name":"Midwest Center for Structural Genomics Argonne National Laboratory Argonne Illinois USA"},{"name":"Structural Biology Center, Biosciences Division Argonne National Laboratory Argonne Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10388"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp255"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr030102i"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01009-09"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70143-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1011715"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70059-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi201449r"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-184036"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.697"},{"key":"e_1_2_7_12_1","article-title":"Structure of apo\u2010 and monometalated forms of NDM\u20101\u2014a highly potent carbapenem\u2010hydrolyzing metallo\u2010\u03b2\u2010lactamase","volume":"6","author":"Kim Y.","year":"2011","journal-title":"PLoS ONE"},{"key":"e_1_2_7_13_1","first-page":"1160","article-title":"Structure of New Delhi metallo\u2010\u03b2\u2010lactamase (NDM\u20101)","volume":"67","author":"Green V. 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