Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).

New Delhi metallo-β-lactmase-1 (NDM-1) has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiot...

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Autores principales:	Bingzheng Shen, Yan Yu, Hui Chen, Xin Cao, Xingzhen Lao, Yongliang Fang, Yun Shi, Jiao Chen, Heng Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d2a33edf2154ec1bc4a2e99cb5063a9
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spelling	oai:doaj.org-article:4d2a33edf2154ec1bc4a2e99cb5063a92021-11-18T07:46:00ZInhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).1932-620310.1371/journal.pone.0062955https://doaj.org/article/4d2a33edf2154ec1bc4a2e99cb5063a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675445/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203New Delhi metallo-β-lactmase-1 (NDM-1) has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiotics have been detected. It could effectively hydrolyze most β-lactams (k cat/K m ratios between 0.03 to 1.28 µmol⁻¹.s⁻¹), except aztreonam. We also found that thiophene-carboxylic acid derivatives could inhibit NDM-1 and have shown synergistic antibacterial activity in combination with meropenem. Flexible docking and quantum mechanics (QM) study revealed electrostatic interactions between the sulfur atom of thiophene-carboxylic acid derivatives and the zinc ion of NDM-1, along with hydrogen bond between inhibitor and His189 of NDM-1. The interaction models proposed here can be used in rational design of NDM-1 inhibitors.Bingzheng ShenYan YuHui ChenXin CaoXingzhen LaoYongliang FangYun ShiJiao ChenHeng ZhengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62955 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bingzheng Shen Yan Yu Hui Chen Xin Cao Xingzhen Lao Yongliang Fang Yun Shi Jiao Chen Heng Zheng Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
description	New Delhi metallo-β-lactmase-1 (NDM-1) has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiotics have been detected. It could effectively hydrolyze most β-lactams (k cat/K m ratios between 0.03 to 1.28 µmol⁻¹.s⁻¹), except aztreonam. We also found that thiophene-carboxylic acid derivatives could inhibit NDM-1 and have shown synergistic antibacterial activity in combination with meropenem. Flexible docking and quantum mechanics (QM) study revealed electrostatic interactions between the sulfur atom of thiophene-carboxylic acid derivatives and the zinc ion of NDM-1, along with hydrogen bond between inhibitor and His189 of NDM-1. The interaction models proposed here can be used in rational design of NDM-1 inhibitors.
format	article
author	Bingzheng Shen Yan Yu Hui Chen Xin Cao Xingzhen Lao Yongliang Fang Yun Shi Jiao Chen Heng Zheng
author_facet	Bingzheng Shen Yan Yu Hui Chen Xin Cao Xingzhen Lao Yongliang Fang Yun Shi Jiao Chen Heng Zheng
author_sort	Bingzheng Shen
title	Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
title_short	Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
title_full	Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
title_fullStr	Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
title_full_unstemmed	Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
title_sort	inhibitor discovery of full-length new delhi metallo-β-lactamase-1 (ndm-1).
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4d2a33edf2154ec1bc4a2e99cb5063a9
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Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).

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