Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations
Cold-adapted enzymes feature a lower thermostability and higher catalytic activity compared to their warm-active homologues, which are considered as a consequence of increased flexibility of their molecular structures. The complexity of the (thermo)stability-flexibility-activity relationship makes i...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1781 |
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| author | Zhi-Bi Zhang Yuan-Ling Xia Guang-Heng Dong Yun-Xin Fu Shu-Qun Liu |
| author_facet | Zhi-Bi Zhang Yuan-Ling Xia Guang-Heng Dong Yun-Xin Fu Shu-Qun Liu |
| author_sort | Zhi-Bi Zhang |
| collection | DOAJ |
| description | Cold-adapted enzymes feature a lower thermostability and higher catalytic activity compared to their warm-active homologues, which are considered as a consequence of increased flexibility of their molecular structures. The complexity of the (thermo)stability-flexibility-activity relationship makes it difficult to define the strategies and formulate a general theory for enzyme cold adaptation. Here, the psychrophilic serine hydroxymethyltransferase (pSHMT) from <i>Psychromonas ingrahamii</i> and its mesophilic counterpart, mSHMT from <i>Escherichia coli</i>, were subjected to μs-scale multiple-replica molecular dynamics (MD) simulations to explore the cold-adaptation mechanism of the dimeric SHMT. The comparative analyses of MD trajectories reveal that pSHMT exhibits larger structural fluctuations and inter-monomer positional movements, a higher global flexibility, and considerably enhanced local flexibility involving the surface loops and active sites. The largest-amplitude motion mode of pSHMT describes the trends of inter-monomer dissociation and enlargement of the active-site cavity, whereas that of mSHMT characterizes the opposite trends. Based on the comparison of the calculated structural parameters and constructed free energy landscapes (FELs) between the two enzymes, we discuss in-depth the physicochemical principles underlying the stability-flexibility-activity relationships and conclude that (i) pSHMT adopts the global-flexibility mechanism to adapt to the cold environment and, (ii) optimizing the protein-solvent interactions and loosening the inter-monomer association are the main strategies for pSHMT to enhance its flexibility. |
| first_indexed | 2024-03-09T04:46:00Z |
| format | Article |
| id | doaj.art-7333e91d45a44ae291db63034c1accbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:46:00Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7333e91d45a44ae291db63034c1accbb2023-12-03T13:15:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224178110.3390/ijms22041781Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics SimulationsZhi-Bi Zhang0Yuan-Ling Xia1Guang-Heng Dong2Yun-Xin Fu3Shu-Qun Liu4State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan & School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan & School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan & School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan & School of Life Sciences, Yunnan University, Kunming 650091, ChinaState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan & School of Life Sciences, Yunnan University, Kunming 650091, ChinaCold-adapted enzymes feature a lower thermostability and higher catalytic activity compared to their warm-active homologues, which are considered as a consequence of increased flexibility of their molecular structures. The complexity of the (thermo)stability-flexibility-activity relationship makes it difficult to define the strategies and formulate a general theory for enzyme cold adaptation. Here, the psychrophilic serine hydroxymethyltransferase (pSHMT) from <i>Psychromonas ingrahamii</i> and its mesophilic counterpart, mSHMT from <i>Escherichia coli</i>, were subjected to μs-scale multiple-replica molecular dynamics (MD) simulations to explore the cold-adaptation mechanism of the dimeric SHMT. The comparative analyses of MD trajectories reveal that pSHMT exhibits larger structural fluctuations and inter-monomer positional movements, a higher global flexibility, and considerably enhanced local flexibility involving the surface loops and active sites. The largest-amplitude motion mode of pSHMT describes the trends of inter-monomer dissociation and enlargement of the active-site cavity, whereas that of mSHMT characterizes the opposite trends. Based on the comparison of the calculated structural parameters and constructed free energy landscapes (FELs) between the two enzymes, we discuss in-depth the physicochemical principles underlying the stability-flexibility-activity relationships and conclude that (i) pSHMT adopts the global-flexibility mechanism to adapt to the cold environment and, (ii) optimizing the protein-solvent interactions and loosening the inter-monomer association are the main strategies for pSHMT to enhance its flexibility.https://www.mdpi.com/1422-0067/22/4/1781cold adaptationmolecular dynamics simulationstability-flexibility-activity relationshipsprotein-solvent interactionsfree energy landscape |
| spellingShingle | Zhi-Bi Zhang Yuan-Ling Xia Guang-Heng Dong Yun-Xin Fu Shu-Qun Liu Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations International Journal of Molecular Sciences cold adaptation molecular dynamics simulation stability-flexibility-activity relationships protein-solvent interactions free energy landscape |
| title | Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations |
| title_full | Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations |
| title_fullStr | Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations |
| title_full_unstemmed | Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations |
| title_short | Exploring the Cold-Adaptation Mechanism of Serine Hydroxymethyltransferase by Comparative Molecular Dynamics Simulations |
| title_sort | exploring the cold adaptation mechanism of serine hydroxymethyltransferase by comparative molecular dynamics simulations |
| topic | cold adaptation molecular dynamics simulation stability-flexibility-activity relationships protein-solvent interactions free energy landscape |
| url | https://www.mdpi.com/1422-0067/22/4/1781 |
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