Key Amino Acids for Transferase Activity of GDSL Lipases
The Gly-Asp-Ser-Leu (GDSL) motif of esterase/lipase family proteins (GELPs) generally exhibit esterase activity, whereas transferase activity is markedly preferred in several GELPs, including the <i>Tanacetum cinerariifolium</i> GDSL lipase TciGLIP, which is responsible for the biosynthe...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15141 |
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| author | Takanori Yamashiro Akira Shiraishi Koji Nakayama Honoo Satake |
| author_facet | Takanori Yamashiro Akira Shiraishi Koji Nakayama Honoo Satake |
| author_sort | Takanori Yamashiro |
| collection | DOAJ |
| description | The Gly-Asp-Ser-Leu (GDSL) motif of esterase/lipase family proteins (GELPs) generally exhibit esterase activity, whereas transferase activity is markedly preferred in several GELPs, including the <i>Tanacetum cinerariifolium</i> GDSL lipase TciGLIP, which is responsible for the biosynthesis of the natural insecticide, pyrethrin I. This transferase activity is due to the substrate affinity regulated by the protein structure and these features are expected to be conserved in transferase activity-exhibiting GELPs (tr-GELPs). In this study, we identified two amino acid residues, [N/R]208 and D484, in GELP sequence alignments as candidate key residues for the transferase activity of tr-GELPs by two-entropy analysis. Molecular phylogenetic analysis demonstrated that each tr-GELP is located in the clusters for non-tr-GELPs, and most GELPs conserve at least one of the two residues. These results suggest that the two conserved residues are required for the acquisition of transferase activity in the GELP family. Furthermore, substrate docking analyses using ColabFold-generated structure models of both natives and each of the two amino acids-mutated TciGLIPs also revealed numerous docking models for the proper access of substrates to the active site, indicating crucial roles of these residues of TciGLIP in its transferase activity. This is the first report on essential residues in tr-GELPs for the transferase activity. |
| first_indexed | 2024-03-09T17:45:47Z |
| format | Article |
| id | doaj.art-b83b69e4d4d145cea9282548791d285d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:47Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b83b69e4d4d145cea9282548791d285d2023-11-24T11:13:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231514110.3390/ijms232315141Key Amino Acids for Transferase Activity of GDSL LipasesTakanori Yamashiro0Akira Shiraishi1Koji Nakayama2Honoo Satake3Dainihon Jochugiku Co., Ltd., 1-1-11 Daikoku-cho, Toyonaka 561-0827, Osaka, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, 8-1-1 Seikadai, Seika-cho, Souraku 619-0284, Kyoto, JapanDainihon Jochugiku Co., Ltd., 1-1-11 Daikoku-cho, Toyonaka 561-0827, Osaka, JapanDepartment of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Hyogo, JapanThe Gly-Asp-Ser-Leu (GDSL) motif of esterase/lipase family proteins (GELPs) generally exhibit esterase activity, whereas transferase activity is markedly preferred in several GELPs, including the <i>Tanacetum cinerariifolium</i> GDSL lipase TciGLIP, which is responsible for the biosynthesis of the natural insecticide, pyrethrin I. This transferase activity is due to the substrate affinity regulated by the protein structure and these features are expected to be conserved in transferase activity-exhibiting GELPs (tr-GELPs). In this study, we identified two amino acid residues, [N/R]208 and D484, in GELP sequence alignments as candidate key residues for the transferase activity of tr-GELPs by two-entropy analysis. Molecular phylogenetic analysis demonstrated that each tr-GELP is located in the clusters for non-tr-GELPs, and most GELPs conserve at least one of the two residues. These results suggest that the two conserved residues are required for the acquisition of transferase activity in the GELP family. Furthermore, substrate docking analyses using ColabFold-generated structure models of both natives and each of the two amino acids-mutated TciGLIPs also revealed numerous docking models for the proper access of substrates to the active site, indicating crucial roles of these residues of TciGLIP in its transferase activity. This is the first report on essential residues in tr-GELPs for the transferase activity.https://www.mdpi.com/1422-0067/23/23/15141<i>Tanacetum cinerariifolium</i>GDSL lipasetransferasein silico |
| spellingShingle | Takanori Yamashiro Akira Shiraishi Koji Nakayama Honoo Satake Key Amino Acids for Transferase Activity of GDSL Lipases International Journal of Molecular Sciences <i>Tanacetum cinerariifolium</i> GDSL lipase transferase in silico |
| title | Key Amino Acids for Transferase Activity of GDSL Lipases |
| title_full | Key Amino Acids for Transferase Activity of GDSL Lipases |
| title_fullStr | Key Amino Acids for Transferase Activity of GDSL Lipases |
| title_full_unstemmed | Key Amino Acids for Transferase Activity of GDSL Lipases |
| title_short | Key Amino Acids for Transferase Activity of GDSL Lipases |
| title_sort | key amino acids for transferase activity of gdsl lipases |
| topic | <i>Tanacetum cinerariifolium</i> GDSL lipase transferase in silico |
| url | https://www.mdpi.com/1422-0067/23/23/15141 |
| work_keys_str_mv | AT takanoriyamashiro keyaminoacidsfortransferaseactivityofgdsllipases AT akirashiraishi keyaminoacidsfortransferaseactivityofgdsllipases AT kojinakayama keyaminoacidsfortransferaseactivityofgdsllipases AT honoosatake keyaminoacidsfortransferaseactivityofgdsllipases |