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Mar. Drugs 2018, 16(12), 471; https://doi.org/10.3390/md16120471

Mutagenesis Studies and Structure-function Relationships for GalNAc/Gal-Specific Lectin from the Sea Mussel Crenomytilus grayanus

1
Laboratory of Marine Biochemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Science, 159, Stoletya Vladivostoku str., Vladivostok 690022, Russia
2
Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Science, 159, Stoletya Vladivostoku str., Vladivostok 690022, Russia
3
Innovative Technology Center, School of Economics and Management, Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690090, Russia
Deceased on 19 March 2018.
*
Author to whom correspondence should be addressed.
Received: 17 October 2018 / Revised: 19 November 2018 / Accepted: 21 November 2018 / Published: 27 November 2018
(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)
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Abstract

The GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus (CGL) with anticancer activity represents а novel lectin family with β-trefoil fold. Earlier, the crystal structures of CGL complexes with globotriose, galactose and galactosamine, and mutagenesis studies have revealed that the lectin contained three carbohydrate-binding sites. The ability of CGL to recognize globotriose (Gb3) on the surface of breast cancer cells and bind mucin-type glycoproteins, which are often associated with oncogenic transformation, makes this compound to be perspective as a biosensor for cancer diagnostics. In this study, we describe results on in silico analysis of binding mechanisms of CGL to ligands (galactose, globotriose and mucin) and evaluate the individual contribution of the amino acid residues from carbohydrate-binding sites to CGL activity by site-directed mutagenesis. The alanine substitutions of His37, His129, Glu75, Asp127, His85, Asn27 and Asn119 affect the CGL mucin-binding activity, indicating their importance in the manifestation of lectin activity. It has been found that CGL affinity to ligands depends on their structure, which is determined by the number of hydrogen bonds in the CGL-ligand complexes. The obtained results should be helpful for understanding molecular machinery of CGL functioning and designing a synthetic analog of CGL with enhanced carbohydrate-binding properties. View Full-Text
Keywords: galactose-specific lectin; Crenomytilus grayanus; carbohydrate-binding site; molecular docking; site-specific mutagenesis; carbohydrate-binding activity galactose-specific lectin; Crenomytilus grayanus; carbohydrate-binding site; molecular docking; site-specific mutagenesis; carbohydrate-binding activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kovalchuk, S.N.; Buinovskaya, N.S.; Likhatskaya, G.N.; Rasskazov, V.A.; Son, O.M.; Tekutyeva, L.A.; Balabanova, L.A. Mutagenesis Studies and Structure-function Relationships for GalNAc/Gal-Specific Lectin from the Sea Mussel Crenomytilus grayanus. Mar. Drugs 2018, 16, 471.

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