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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675445/pdf/?tool=EBI |
| _version_ | 1818458673828069376 |
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| 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 |
| collection | DOAJ |
| 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. |
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| format | Article |
| id | doaj.art-4d2a33edf2154ec1bc4a2e99cb5063a9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:02:12Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-4d2a33edf2154ec1bc4a2e99cb5063a92022-12-21T22:44:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6295510.1371/journal.pone.0062955Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).Bingzheng ShenYan YuHui ChenXin CaoXingzhen LaoYongliang FangYun ShiJiao ChenHeng ZhengNew 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675445/pdf/?tool=EBI |
| spellingShingle | 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). PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675445/pdf/?tool=EBI |
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