Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity
In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in can...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/6/1009 |
| _version_ | 1811254654965645312 |
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| author | Paolo Piazzetta Tiziana Marino Nino Russo |
| author_facet | Paolo Piazzetta Tiziana Marino Nino Russo |
| author_sort | Paolo Piazzetta |
| collection | DOAJ |
| description | In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in cancer therapy. The study has been performed within the framework of three-layer ONIOM (QM-high:QM’-medium:MM-low) hybrid approach. The computations revealed that the hydrolysis process is not energetically favored, in agreement with the observed weak carbonic anhydrase’s esterase activity. |
| first_indexed | 2024-04-12T17:10:53Z |
| format | Article |
| id | doaj.art-20b18d95c58545a3b446a00f0f22c27d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T17:10:53Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-20b18d95c58545a3b446a00f0f22c27d2022-12-22T03:23:47ZengMDPI AGMolecules1420-30492017-06-01226100910.3390/molecules22061009molecules22061009Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase ActivityPaolo Piazzetta0Tiziana Marino1Nino Russo2Dipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, 87036 Arcavacata di Rende (CS), ItalyDipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, 87036 Arcavacata di Rende (CS), ItalyDipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, 87036 Arcavacata di Rende (CS), ItalyIn order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in cancer therapy. The study has been performed within the framework of three-layer ONIOM (QM-high:QM’-medium:MM-low) hybrid approach. The computations revealed that the hydrolysis process is not energetically favored, in agreement with the observed weak carbonic anhydrase’s esterase activity.http://www.mdpi.com/1420-3049/22/6/1009carbonic anhydraseDFTenzyme promiscuityenzyme inhibitors |
| spellingShingle | Paolo Piazzetta Tiziana Marino Nino Russo Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity Molecules carbonic anhydrase DFT enzyme promiscuity enzyme inhibitors |
| title | Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity |
| title_full | Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity |
| title_fullStr | Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity |
| title_full_unstemmed | Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity |
| title_short | Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity |
| title_sort | mechanistic explanation of the weak carbonic anhydrase s esterase activity |
| topic | carbonic anhydrase DFT enzyme promiscuity enzyme inhibitors |
| url | http://www.mdpi.com/1420-3049/22/6/1009 |
| work_keys_str_mv | AT paolopiazzetta mechanisticexplanationoftheweakcarbonicanhydrasesesteraseactivity AT tizianamarino mechanisticexplanationoftheweakcarbonicanhydrasesesteraseactivity AT ninorusso mechanisticexplanationoftheweakcarbonicanhydrasesesteraseactivity |