Crystal structure and kinetic analysis of the class B3 di-zinc metallo-β-lactamase LRA-12 from an Alaskan soil metagenome
Publication Date
July 27, 2017
Authors
María Margarita Rodríguez, Raphaël Herman, Barbara Ghiglione, Frédéric Kerff, et al
Volume
12
Issue
7
Pages
e0182043
DOI
https://dx.plos.org/10.1371/journal.pone.0182043
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0182043
Scopus
85026450201
Mendeley
http://www.mendeley.com/research/crystal-structure-kinetic-analysis-class-b3-dizinc-metallo%CE%B2lactamase-lra12-alaskan-soil-metagenome
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Mendeley | Further Information

{"title"=>"Crystal structure and kinetic analysis of the class B3 di-zinc metallo-β-lactamase LRA-12 from an Alaskan soil metagenome", "type"=>"journal", "authors"=>[{"first_name"=>"María Margarita", "last_name"=>"Rodríguez", "scopus_author_id"=>"7404258884"}, {"first_name"=>"Raphaël", "last_name"=>"Herman", "scopus_author_id"=>"55107042100"}, {"first_name"=>"Barbara", "last_name"=>"Ghiglione", "scopus_author_id"=>"36481161100"}, {"first_name"=>"Frédéric", "last_name"=>"Kerff", "scopus_author_id"=>"6505906377"}, {"first_name"=>"Gabriela", "last_name"=>"D’Amico González", "scopus_author_id"=>"57195242012"}, {"first_name"=>"Fabrice", "last_name"=>"Bouillenne", "scopus_author_id"=>"6507984925"}, {"first_name"=>"Moreno", "last_name"=>"Galleni", "scopus_author_id"=>"7005720924"}, {"first_name"=>"Jo", "last_name"=>"Handelsman", "scopus_author_id"=>"7005267687"}, {"first_name"=>"Paulette", "last_name"=>"Charlier", "scopus_author_id"=>"56210348200"}, {"first_name"=>"Gabriel", "last_name"=>"Gutkind", "scopus_author_id"=>"7004667293"}, {"first_name"=>"Eric", "last_name"=>"Sauvage", "scopus_author_id"=>"6602995332"}, {"first_name"=>"Pablo", "last_name"=>"Power", "scopus_author_id"=>"7102946066"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"85026450201", "doi"=>"10.1371/journal.pone.0182043", "pui"=>"617563355", "scopus"=>"2-s2.0-85026450201", "issn"=>"19326203", "isbn"=>"1111111111"}, "id"=>"e4569e13-dcc1-3d69-9f42-3db6a235baea", "abstract"=>"© 2017 Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. We analyzed the kinetic properties of the metagenomic class B3 β-lactamase LRA-12, and determined its crystallographic structure in order to compare it with prevalent metallo-β-lac-tamases (MBLs) associated with clinical pathogens. We showed that LRA-12 confers extended-spectrum resistance on E. coli when expressed from recombinant clones, and the MIC values for carbapenems were similar to those observed in enterobacteria expressing plasmid-borne MBLs such as VIM, IMP or NDM. This was in agreement with the strong carbapenemase activity displayed by LRA-12, similar to GOB β-lactamases. Among the chelating agents evaluated, dipicolinic acid inhibited the enzyme more strongly than EDTA, which required pre-incubation with the enzyme to achieve measurable inhibition. Structurally, LRA-12 contains the conserved main structural features of di-zinc class B β-lactamases, and presents unique structural signatures that differentiate this enzyme from others within the family: (i) two loops (α3-β7 and β11-α5) that could influence antibiotic entrance and remodeling of the active site cavity; (ii) a voluminous catalytic cavity probably responsible for the high hydrolytic efficiency of the enzyme; (iii) the absence of disulfide bridges; (iv) a unique Gln116 at metal-binding site 1; (v) a methionine residue at position 221that replaces Cys/Ser found in other B3 β-lactamases in a predominantly hydrophobic environment, likely playing a role in protein stability. The structure of LRA-12 indicates that MBLs exist in wild microbial populations in extreme environments, or environments with low anthropic impact, and under the appropriate antibiotic selective pressure could be captured and disseminated to pathogens.", "link"=>"http://www.mendeley.com/research/crystal-structure-kinetic-analysis-class-b3-dizinc-metallo%CE%B2lactamase-lra12-alaskan-soil-metagenome", "reader_count"=>5, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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