Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.

The New Delhi Metallo-β-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known β-lactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed...

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Autores principales:	Youngchang Kim, Christine Tesar, Joseph Mire, Robert Jedrzejczak, Andrew Binkowski, Gyorgy Babnigg, James Sacchettini, Andrzej Joachimiak
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb105b64899e41dd9b493fb98818bf62
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spelling	oai:doaj.org-article:cb105b64899e41dd9b493fb98818bf622021-11-04T06:08:59ZStructure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.1932-620310.1371/journal.pone.0024621https://doaj.org/article/cb105b64899e41dd9b493fb98818bf622011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931780/?tool=EBIhttps://doaj.org/toc/1932-6203The New Delhi Metallo-β-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known β-lactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed that NDM-1 is capable of efficiently hydrolyzing a wide range of β-lactams, including many carbapenems considered as "last resort" antibiotics. The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-β-lactamase. This site is capable of accommodating many β-lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent β-lactamase. Indeed, five loops contribute "keg" residues in the active site including side chains involved in metal binding. Loop 1 in particular, shows conformational flexibility, apparently related to the acceptance and positioning of substrates for cleavage by a zinc-activated water molecule.Youngchang KimChristine TesarJoseph MireRobert JedrzejczakAndrew BinkowskiGyorgy BabniggJames SacchettiniAndrzej JoachimiakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24621 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Youngchang Kim Christine Tesar Joseph Mire Robert Jedrzejczak Andrew Binkowski Gyorgy Babnigg James Sacchettini Andrzej Joachimiak Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
description	The New Delhi Metallo-β-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known β-lactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed that NDM-1 is capable of efficiently hydrolyzing a wide range of β-lactams, including many carbapenems considered as "last resort" antibiotics. The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-β-lactamase. This site is capable of accommodating many β-lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent β-lactamase. Indeed, five loops contribute "keg" residues in the active site including side chains involved in metal binding. Loop 1 in particular, shows conformational flexibility, apparently related to the acceptance and positioning of substrates for cleavage by a zinc-activated water molecule.
format	article
author	Youngchang Kim Christine Tesar Joseph Mire Robert Jedrzejczak Andrew Binkowski Gyorgy Babnigg James Sacchettini Andrzej Joachimiak
author_facet	Youngchang Kim Christine Tesar Joseph Mire Robert Jedrzejczak Andrew Binkowski Gyorgy Babnigg James Sacchettini Andrzej Joachimiak
author_sort	Youngchang Kim
title	Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
title_short	Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
title_full	Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
title_fullStr	Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
title_full_unstemmed	Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
title_sort	structure of apo- and monometalated forms of ndm-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cb105b64899e41dd9b493fb98818bf62
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Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-β-lactamase.

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