{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:59:31Z","timestamp":1792004371885,"version":"4.4.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Carbapenems are one of the last lines of defense for Gram-negative pathogens, such as members of the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            . Despite the fact that most carbapenems are resistant to extended-spectrum \u03b2-lactamase (ESBL), emerging metallo-\u03b2-lactamases (MBLs), including New Delhi metallo-\u03b2-lactamase 1 (NDM-1), that can hydrolyze carbapenems have become prevalent and are frequently associated with the so-called \u201csuperbugs,\u201d for which treatments are extremely limited. Crystallographic study sheds light on the modes of antibiotic binding to NDM-1, yet the mechanisms governing substrate recognition and specificity are largely unclear. This study provides a connection between crystallographic study and the functional significance of NDM-1, with an emphasis on the substrate specificity and catalysis of various \u03b2-lactams. L1 loop residues L\n            <jats:sup>59<\/jats:sup>\n            , V\n            <jats:sup>67<\/jats:sup>\n            , and W\n            <jats:sup>87<\/jats:sup>\n            were important for the activity of NDM-1, most likely through maintaining the partial folding of the L1 loop or active site conformation through hydrophobic interaction with the R groups of \u03b2-lactams or the \u03b2-lactam ring. Substitution of alanine for L\n            <jats:sup>59<\/jats:sup>\n            showed greater reduction of MICs to ampicillin and selected cephalosporins, whereas substitutions of alanine for V\n            <jats:sup>67<\/jats:sup>\n            had more impact on the MICs of carbapenems. K\n            <jats:sup>224<\/jats:sup>\n            and N\n            <jats:sup>233<\/jats:sup>\n            on the L3 loop played important roles in the recognition of substrate and contributed to substrate hydrolysis. These data together with the structure comparison of the B1 and B2 subclasses of MBLs revealed that the broad substrate specificity of NDM-1 could be due to the ability of its wide active site cavity to accommodate a wide range of \u03b2-lactams. This study provides insights into the development of efficient inhibitors for NDM-1 and offers an efficient tactic with which to study the substrate specificities of other \u03b2-lactamases.\n          <\/jats:p>","DOI":"10.1128\/aac.01977-13","type":"journal-article","created":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T14:43:52Z","timestamp":1404225832000},"page":"5372-5378","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Molecular Mechanisms of Substrate Recognition and Specificity of New Delhi Metallo-\u03b2-Lactamase"],"prefix":"10.1128","volume":"58","author":[{"given":"Jiachi","family":"Chiou","sequence":"first","affiliation":[{"name":"State Key Lab of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR; Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Yun-Chung","family":"Leung","sequence":"additional","affiliation":[{"name":"State Key Lab of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR; Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Lab of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR; Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.09.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1211"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01009-09"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102911"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi971056h"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.7.2347-2349.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-09"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00774-09"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.660-663.2001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.11.012"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi992569m"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.01.003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444997010627"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-184036"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3630687"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990356r"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja303579d"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.041093405"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(03)00070-X"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm701031n"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01336-09"},{"key":"e_1_3_3_23_2","volume-title":"Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement:","author":"CLSI","year":"2011","unstructured":"CLSI. 2011. Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement: Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci3001277"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi201449r"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024621"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0305303"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00340-11"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060893t"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.ps.40884"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023606"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.10.070"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01977-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01977-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:49:06Z","timestamp":1645483746000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01977-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1128\/AAC.01977-13"],"URL":"https:\/\/doi.org\/10.1128\/aac.01977-13","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9]]},"assertion":[{"value":"2013-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}