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Both strains harbored the plasmid-contained\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>TEM-1<\/jats:sub>\n            and\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC-2<\/jats:sub>\n            genes.\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KLUC-2<\/jats:sub>\n            , encoding a mutant of the chromosomal \u03b2-lactamase of\n            <jats:italic>Kluyvera cryocrescens<\/jats:italic>\n            , was also identified at a plasmid location in\n            <jats:italic>E. cloacae<\/jats:italic>\n            7506, suggesting the IS\n            <jats:italic>Ecp1<\/jats:italic>\n            -assisted escape of\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KLUC<\/jats:sub>\n            from the chromosome. Determination of the KPC-2 structure at 1.6 A\u030a revealed that the binding site was occupied by the C-terminal (C-ter) residues coming from a symmetric KPC-2 monomer, with the ultimate C-ter Glu interacting with Ser130, Lys234, Thr235, and Thr237 in the active site. This mode of binding can be paralleled to the inhibition of the TEM-1 \u03b2-lactamase by the inhibitory protein BLIP. Determination of the 1.23-A\u030a structure of a KPC-2 mutant in which the five C-ter residues were deleted revealed that the catalytic site was filled by a citrate molecule. Structure analysis and docking simulations with cefotaxime and imipenem provided further insights into the molecular basis of the extremely broad spectrum of KPC-2, which behaves as a cefotaximase with significant activity against carbapenems. In particular, residues 104, 105, 132, and 167 draw a binding cavity capable of accommodating both the aminothiazole moiety of cefotaxime and the 6\u03b1-hydroxyethyl group of imipenem, with the binding of the former drug being also favored by a significant degree of freedom at the level of the loop at positions 96 to 105 and by an enlargement of the binding site at the end of strand \u03b23.\n          <\/jats:p>","DOI":"10.1128\/aac.00163-08","type":"journal-article","created":{"date-parts":[[2008,7,15]],"date-time":"2008-07-15T00:45:06Z","timestamp":1216082706000},"page":"3725-3736","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["Genetic and Structural Insights into the Dissemination Potential of the Extremely Broad-Spectrum Class A \u03b2-Lactamase KPC-2 Identified in an\n            <i>Escherichia coli<\/i>\n            Strain and an\n            <i>Enterobacter cloacae<\/i>\n            Strain Isolated from the Same Patient in France"],"prefix":"10.1128","volume":"52","author":[{"given":"Stephanie","family":"Petrella","sequence":"first","affiliation":[{"name":"UPMC Univ Paris 06, EA1541, Bacteriologie-Hygie\u0300ne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Ziental-Gelus","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, LRMA, INSERM, UMRS 872-12"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Mayer","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, LRMA, INSERM, UMRS 872-12"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle","family":"Renard","sequence":"additional","affiliation":[{"name":"AP-HP, Ho\u0302pital Pitie\u0301-Salpe\u0302trie\u0300re, Bacte\u0301riologie-Hygie\u0300ne, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jarlier","sequence":"additional","affiliation":[{"name":"UPMC Univ Paris 06, EA1541, Bacteriologie-Hygie\u0300ne"},{"name":"AP-HP, Ho\u0302pital Pitie\u0301-Salpe\u0302trie\u0300re, Bacte\u0301riologie-Hygie\u0300ne, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wladimir","family":"Sougakoff","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, LRMA, INSERM, UMRS 872-12"},{"name":"AP-HP, Ho\u0302pital Pitie\u0301-Salpe\u0302trie\u0300re, Bacte\u0301riologie-Hygie\u0300ne, F-75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00015-07"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2510073"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/7.6.1513"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg256"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.7.1936-1942.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/12.4.313"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/421495"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.776-778.2005"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540040211"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444998003254"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1211"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.02.010"},{"key":"e_1_3_2_15_2","unstructured":"Cornish-Bowden A. 1995. 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