sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process
Secreted phospholipases A2 (sPLA2s) are peripheral membrane enzymes that hydrolyze phospholipids in the <i>sn-2</i> position. The action of sPLA2 is associated with the work of two active sites. One, the interface binding site (IBS), is needed to bind the enzyme to the membrane surface....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/10/669 |
| _version_ | 1827647880260747264 |
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| author | Natalia Kuzmina Pavel Volynsky Ivan Boldyrev Anna Alekseeva |
| author_facet | Natalia Kuzmina Pavel Volynsky Ivan Boldyrev Anna Alekseeva |
| author_sort | Natalia Kuzmina |
| collection | DOAJ |
| description | Secreted phospholipases A2 (sPLA2s) are peripheral membrane enzymes that hydrolyze phospholipids in the <i>sn-2</i> position. The action of sPLA2 is associated with the work of two active sites. One, the interface binding site (IBS), is needed to bind the enzyme to the membrane surface. The other one, the catalytic site, is needed to hydrolyze the substrate. The interplay between sites, how the substrate protrudes to, and how the hydrolysis products release from, the catalytic site remains in the focus of investigations. Here, we report that bee venom PLA2 has two additional interface binding modes and enzyme activity through constant switching between three different orientations (modes of binding), only one of which is responsible for substrate uptake from the bilayer. The finding was obtained independently using atomic force microscopy and molecular dynamics. Switching between modes has biological significance: modes are steps of the enzyme moving along the membrane, product release in biological milieu, and enzyme desorption from the bilayer surface. |
| first_indexed | 2024-03-09T19:24:48Z |
| format | Article |
| id | doaj.art-4f28753b7c3b4b38ad7523acae63307e |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T19:24:48Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-4f28753b7c3b4b38ad7523acae63307e2023-11-24T02:58:47ZengMDPI AGToxins2072-66512022-09-01141066910.3390/toxins14100669sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis ProcessNatalia Kuzmina0Pavel Volynsky1Ivan Boldyrev2Anna Alekseeva3Frumkin Institute of Physical chemistry and Electrochemistry, Russian Academy of Sciences, 119071 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaSecreted phospholipases A2 (sPLA2s) are peripheral membrane enzymes that hydrolyze phospholipids in the <i>sn-2</i> position. The action of sPLA2 is associated with the work of two active sites. One, the interface binding site (IBS), is needed to bind the enzyme to the membrane surface. The other one, the catalytic site, is needed to hydrolyze the substrate. The interplay between sites, how the substrate protrudes to, and how the hydrolysis products release from, the catalytic site remains in the focus of investigations. Here, we report that bee venom PLA2 has two additional interface binding modes and enzyme activity through constant switching between three different orientations (modes of binding), only one of which is responsible for substrate uptake from the bilayer. The finding was obtained independently using atomic force microscopy and molecular dynamics. Switching between modes has biological significance: modes are steps of the enzyme moving along the membrane, product release in biological milieu, and enzyme desorption from the bilayer surface.https://www.mdpi.com/2072-6651/14/10/669PLA2lipidshydrolysisAFMsupported lipid bilayersmolecular dynamics |
| spellingShingle | Natalia Kuzmina Pavel Volynsky Ivan Boldyrev Anna Alekseeva sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process Toxins PLA2 lipids hydrolysis AFM supported lipid bilayers molecular dynamics |
| title | sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process |
| title_full | sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process |
| title_fullStr | sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process |
| title_full_unstemmed | sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process |
| title_short | sPLA2 Wobbles on the Lipid Bilayer between Three Positions, Each Involved in the Hydrolysis Process |
| title_sort | spla2 wobbles on the lipid bilayer between three positions each involved in the hydrolysis process |
| topic | PLA2 lipids hydrolysis AFM supported lipid bilayers molecular dynamics |
| url | https://www.mdpi.com/2072-6651/14/10/669 |
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