Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1

Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on the São Paulo MBL (SPM-1), which reveal its Zn(ii) ion usage and mechanism as characteristic of the clinically important di-Zn(ii) dependent B1 MBL subfamily. Biophysi...

Descripción completa

Detalles Bibliográficos
Autores principales: Brem, Jürgen, Struwe, Weston B., Rydzik, Anna M., Tarhonskaya, Hanna, Pfeffer, Inga, Flashman, Emily, van Berkel, Sander S., Spencer, James, Claridge, Timothy D. W., McDonough, Michael A., Benesch, Justin L. P., Schofield, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333608/
https://www.ncbi.nlm.nih.gov/pubmed/25717359
http://dx.doi.org/10.1039/c4sc01752h
_version_ 1782358069741617152
author Brem, Jürgen
Struwe, Weston B.
Rydzik, Anna M.
Tarhonskaya, Hanna
Pfeffer, Inga
Flashman, Emily
van Berkel, Sander S.
Spencer, James
Claridge, Timothy D. W.
McDonough, Michael A.
Benesch, Justin L. P.
Schofield, Christopher J.
author_facet Brem, Jürgen
Struwe, Weston B.
Rydzik, Anna M.
Tarhonskaya, Hanna
Pfeffer, Inga
Flashman, Emily
van Berkel, Sander S.
Spencer, James
Claridge, Timothy D. W.
McDonough, Michael A.
Benesch, Justin L. P.
Schofield, Christopher J.
author_sort Brem, Jürgen
collection PubMed
description Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on the São Paulo MBL (SPM-1), which reveal its Zn(ii) ion usage and mechanism as characteristic of the clinically important di-Zn(ii) dependent B1 MBL subfamily. Biophysical analyses employing crystallography, dynamic (19)F NMR and ion mobility mass spectrometry, however, reveal that SPM-1 possesses loop and mobile element regions characteristic of the B2 MBLs. These include a mobile α3 region which is important in catalysis and determining inhibitor selectivity. SPM-1 thus appears to be a hybrid B1/B2 MBL. The results have implications for MBL evolution and inhibitor design.
format Online
Article
Text
id pubmed-4333608
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-43336082015-02-23 Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1 Brem, Jürgen Struwe, Weston B. Rydzik, Anna M. Tarhonskaya, Hanna Pfeffer, Inga Flashman, Emily van Berkel, Sander S. Spencer, James Claridge, Timothy D. W. McDonough, Michael A. Benesch, Justin L. P. Schofield, Christopher J. Chem Sci Chemistry Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibiotics. We report biophysical and kinetic studies on the São Paulo MBL (SPM-1), which reveal its Zn(ii) ion usage and mechanism as characteristic of the clinically important di-Zn(ii) dependent B1 MBL subfamily. Biophysical analyses employing crystallography, dynamic (19)F NMR and ion mobility mass spectrometry, however, reveal that SPM-1 possesses loop and mobile element regions characteristic of the B2 MBLs. These include a mobile α3 region which is important in catalysis and determining inhibitor selectivity. SPM-1 thus appears to be a hybrid B1/B2 MBL. The results have implications for MBL evolution and inhibitor design. Royal Society of Chemistry 2015-02-01 2014-10-24 /pmc/articles/PMC4333608/ /pubmed/25717359 http://dx.doi.org/10.1039/c4sc01752h Text en This journal is © The Royal Society of Chemistry 2014 http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Brem, Jürgen
Struwe, Weston B.
Rydzik, Anna M.
Tarhonskaya, Hanna
Pfeffer, Inga
Flashman, Emily
van Berkel, Sander S.
Spencer, James
Claridge, Timothy D. W.
McDonough, Michael A.
Benesch, Justin L. P.
Schofield, Christopher J.
Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title_full Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title_fullStr Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title_full_unstemmed Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title_short Studying the active-site loop movement of the São Paolo metallo-β-lactamase-1
title_sort studying the active-site loop movement of the são paolo metallo-β-lactamase-1
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333608/
https://www.ncbi.nlm.nih.gov/pubmed/25717359
http://dx.doi.org/10.1039/c4sc01752h
work_keys_str_mv AT bremjurgen studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT struwewestonb studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT rydzikannam studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT tarhonskayahanna studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT pfefferinga studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT flashmanemily studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT vanberkelsanders studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT spencerjames studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT claridgetimothydw studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT mcdonoughmichaela studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT beneschjustinlp studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1
AT schofieldchristopherj studyingtheactivesiteloopmovementofthesaopaolometalloblactamase1

Ejemplares similares