New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa
AbstractSea 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. View Full-Text
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Gladkikh, I.; Monastyrnaya, M.; Zelepuga, E.; Sintsova, O.; Tabakmakher, V.; Gnedenko, O.; Ivanov, A.; Hua, K.-F.; Kozlovskaya, E. New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa. Mar. Drugs 2015, 13, 6038-6063.
Gladkikh I, Monastyrnaya M, Zelepuga E, Sintsova O, Tabakmakher V, Gnedenko O, Ivanov A, Hua K-F, Kozlovskaya E. New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa. Marine Drugs. 2015; 13(10):6038-6063.Chicago/Turabian Style
Gladkikh, Irina; Monastyrnaya, Margarita; Zelepuga, Elena; Sintsova, Oksana; Tabakmakher, Valentin; Gnedenko, Oksana; Ivanov, Alexis; Hua, Kuo-Feng; Kozlovskaya, Emma. 2015. "New Kunitz-Type HCRG Polypeptides from the Sea Anemone Heteractis crispa." Mar. Drugs 13, no. 10: 6038-6063.