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大花生菜种子凝集素的血管舒张活性:结构分析。

Vasorelaxant activity of Canavalia grandiflora seed lectin: A structural analysis.

机构信息

Laboratório de Moléculas Biologicamente Ativas, Universidade Federal do Ceará, Fortaleza, Brazil.

Laboratório de Moléculas Biologicamente Ativas, Universidade Federal do Ceará, Fortaleza, Brazil; Departamento de Engenharia de Pesca, Universidade Federal do Ceará, Fortaleza, Brazil.

出版信息

Arch Biochem Biophys. 2014 Feb 1;543:31-9. doi: 10.1016/j.abb.2013.12.006. Epub 2013 Dec 17.

DOI:10.1016/j.abb.2013.12.006
PMID:24361256
Abstract

Lectins are comprised of a large family of proteins capable of the specific and reversible recognition of carbohydrates. Legume lectins, the most studied plant lectins, show high structural similarity, but with modifications that imply a variation in the intensity of some biological activities. In this work, the primary and tertiary structures of Canavalia grandiflora (ConGF) were determined. ConGF, a lectin isolated from C. grandiflora seeds, is able to induce relaxant activity in rat aortic rings. The complete sequence of ConGF comprises 237 amino acids. This particular protein has primary sequence variations commonly found in lectins from Dioclea and Canavalia genera. The protein structure was solved at 2.3 Å resolution by X-ray crystallography. An X-Man molecule was modeled into the carbohydrate recognition domain. Still, ConGF (30 and 100 μg mL(-1)) elicited 25% of vasorelaxation (IC50=34.48 ± 5.07 μg mL(-1)) in endothelialized aortic rings. A nonselective inhibitor of nitric oxide blocked ConGF relaxant effect, showing mediation by nitric oxide. Key distances between ConGF carbohydrate recognition domain residues were determined in order to explain this effect, in turn revealing some structural aspects that could differentiate lectins from the Canavalia genera with respect to different efficacy in vasorelaxant effect.

摘要

凝集素是一大类能够特异性和可逆识别碳水化合物的蛋白质。豆科凝集素是研究最多的植物凝集素,它们具有高度的结构相似性,但存在修饰,这意味着某些生物学活性的强度有所变化。在这项工作中,测定了大花旋花(Canavalia grandiflora)(ConGF)的一级和三级结构。ConGF 是从大花旋花种子中分离出来的一种凝集素,能够诱导大鼠主动脉环产生松弛活性。ConGF 的完整序列由 237 个氨基酸组成。该蛋白具有初级序列变异,通常存在于 Dioclea 和 Canavalia 属的凝集素中。通过 X 射线晶体学,以 2.3 Å 的分辨率解决了该蛋白的结构。X-Man 分子被建模到碳水化合物识别域中。尽管如此,ConGF(30 和 100 μg mL(-1)) 在血管内皮化的主动脉环中引起 25%的血管舒张(IC50=34.48 ± 5.07 μg mL(-1))。一氧化氮的非选择性抑制剂阻断了 ConGF 的舒张作用,表明一氧化氮介导了这种作用。为了解释这种效应,确定了 ConGF 碳水化合物识别域残基之间的关键距离,这反过来又揭示了一些结构方面的差异,这些差异可能使 Canavalia 属的凝集素在血管舒张效应的不同功效方面有所不同。

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