New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa
Sea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily ha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-09-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/10/6038 |
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| author | Irina Gladkikh Margarita Monastyrnaya Elena Zelepuga Oksana Sintsova Valentin Tabakmakher Oksana Gnedenko Alexis Ivanov Kuo-Feng Hua Emma Kozlovskaya |
| author_facet | Irina Gladkikh Margarita Monastyrnaya Elena Zelepuga Oksana Sintsova Valentin Tabakmakher Oksana Gnedenko Alexis Ivanov Kuo-Feng Hua Emma Kozlovskaya |
| author_sort | Irina Gladkikh |
| collection | DOAJ |
| description | Sea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily have been isolated from the sea anemone Heteractis crispa. The amino acid sequences of HCRG1 and HCRG2 identified using the Edman degradation method share up to 95% of their identity with the representatives of the HCGS polypeptide multigene subfamily derived from H. crispa cDNA. Polypeptides are characterized by positively charged Arg at the N-terminus as well as P1 Lys residue at their canonical binding loop, identical to those of bovine pancreatic trypsin inhibitor (BPTI). These polypeptides are shown by our current evidence to be more potent inhibitors of trypsin than the known representatives of the HCGS subfamily with P1Thr. The kinetic and thermodynamic characteristics of the intermolecular interactions between inhibitors and serine proteases were determined by the surface plasmon resonance (SPR) method. Residues functionally important for polypeptide binding to trypsin were revealed using molecular modeling methods. Furthermore, HCRG1 and HCRG2 possess anti-inflammatory activity, reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) secretions, as well as proIL-1β expression in lipopolysaccharide (LPS)-activated macrophages. However, there was no effect on nitric oxide (NO) generation. |
| first_indexed | 2024-04-14T04:32:23Z |
| format | Article |
| id | doaj.art-fcb6c6c1946d4fb4a4c4709bd47ab617 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-14T04:32:23Z |
| publishDate | 2015-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-fcb6c6c1946d4fb4a4c4709bd47ab6172022-12-22T02:12:01ZengMDPI AGMarine Drugs1660-33972015-09-0113106038606310.3390/md13106038md13106038New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispaIrina Gladkikh0Margarita Monastyrnaya1Elena Zelepuga2Oksana Sintsova3Valentin Tabakmakher4Oksana Gnedenko5Alexis Ivanov6Kuo-Feng Hua7Emma Kozlovskaya8Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaElyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaElyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaElyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaElyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaOrekhovich Institute of Biomedical Chemistry, Russian Academy of Sciences, 10, Pogodinskaya Street, Moscow 119121, RussiaOrekhovich Institute of Biomedical Chemistry, Russian Academy of Sciences, 10, Pogodinskaya Street, Moscow 119121, RussiaDepartment of Biotechnology and Animal Science, National Ilan University, No. 1, Section 1, Shen-Lung road, Ilan 260, TaiwanElyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159, Pr. 100 let Vladivostoku, Vladivostok 690022, RussiaSea anemones are a rich source of Kunitz-type polypeptides that possess not only protease inhibitor activity, but also Kv channels toxicity, analgesic, antihistamine, and anti-inflammatory activities. Two Kunitz-type inhibitors belonging to a new Heteractis crispa RG (HCRG) polypeptide subfamily have been isolated from the sea anemone Heteractis crispa. The amino acid sequences of HCRG1 and HCRG2 identified using the Edman degradation method share up to 95% of their identity with the representatives of the HCGS polypeptide multigene subfamily derived from H. crispa cDNA. Polypeptides are characterized by positively charged Arg at the N-terminus as well as P1 Lys residue at their canonical binding loop, identical to those of bovine pancreatic trypsin inhibitor (BPTI). These polypeptides are shown by our current evidence to be more potent inhibitors of trypsin than the known representatives of the HCGS subfamily with P1Thr. The kinetic and thermodynamic characteristics of the intermolecular interactions between inhibitors and serine proteases were determined by the surface plasmon resonance (SPR) method. Residues functionally important for polypeptide binding to trypsin were revealed using molecular modeling methods. Furthermore, HCRG1 and HCRG2 possess anti-inflammatory activity, reducing tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) secretions, as well as proIL-1β expression in lipopolysaccharide (LPS)-activated macrophages. However, there was no effect on nitric oxide (NO) generation.http://www.mdpi.com/1660-3397/13/10/6038sea anemoneKunitz-type protease inhibitorsstructurefunctionSPRanti-inflammatory activity |
| spellingShingle | Irina Gladkikh Margarita Monastyrnaya Elena Zelepuga Oksana Sintsova Valentin Tabakmakher Oksana Gnedenko Alexis Ivanov Kuo-Feng Hua Emma Kozlovskaya New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa Marine Drugs sea anemone Kunitz-type protease inhibitors structure function SPR anti-inflammatory activity |
| title | New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa |
| title_full | New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa |
| title_fullStr | New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa |
| title_full_unstemmed | New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa |
| title_short | New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa |
| title_sort | new kunitz type hcrg polypeptides from the sea anemone heteractis crispa |
| topic | sea anemone Kunitz-type protease inhibitors structure function SPR anti-inflammatory activity |
| url | http://www.mdpi.com/1660-3397/13/10/6038 |
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