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Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of \u03b2\u2010lactamases will help improve the future design of new generation antibiotics and mechanism\u2010based inhibitors of these enzymes. Here we report the construction of a large murine single chain fragment variable (scFv) phage display library of size 2.7 \u00d7 10<jats:sup>9<\/jats:sup> with extended diversity by combining different mouse models. We have used two molecularly different inhibitors of the R\u2010TEM \u03b2\u2010lactamase as targets for selection of catalytic antibodies with \u03b2\u2010lactamase activity. This novel methodology has led to the isolation of five antibody fragments, which are all capable of hydrolyzing the \u03b2\u2010lactam ring. Structural modeling of the selected scFv has revealed the presence of different motifs in each of the antibody fragments potentially responsible for their catalytic activity. Our results confirm (a) the validity of using our two target inhibitors for the <jats:italic>in vitro<\/jats:italic> selection of catalytic antibodies endowed with \u03b2\u2010lactamase activity, and (b) the plasticity of the \u03b2\u2010lactamase active site responsible for the wide resistance of these enzymes to clinically available inhibitors and antibiotics.<\/jats:p>","DOI":"10.1111\/febs.14012","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T12:28:36Z","timestamp":1484137716000},"page":"634-653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Multitarget selection of catalytic antibodies with \u03b2\u2010lactamase activity using phage display"],"prefix":"10.1111","volume":"284","author":[{"given":"Melody A.","family":"Shahsavarian","sequence":"first","affiliation":[{"name":"G\u00e9nie Enzymatique et Cellulaire (GEC) FRE 3580 CNRS Universit\u00e9 de Technologie de 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