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首页> 外文期刊>Biochemistry >Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: Implications for the design of synthetic sweeteners
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Cocrystal structures of NC6.8 Fab identify key interactions for high potency sweetener recognition: Implications for the design of synthetic sweeteners

机译:NC6.8 Fab的共晶结构确定了高效甜味剂识别的关键相互作用:对合成甜味剂设计的启示

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摘要

The crystal structures of the murine monoclonal IgG2b(kappa) antibody NC6.8 Fab fragment complexed with high-potency sweetener compound SC45647 and nontasting high-affinity antagonist TES have been determined. The crystal structures show how sweetener potency is fine-tuned by multiple interactions between specific receptor residues and the functionally different groups of the sweeteners. Comparative analysis with the structure of NC6.8 complexed with the super-potency sweetener NC174 reveals that although the same residues in the antigen binding pocket of NC6.8 interact with the zwitterionic, trisubstituted guanidinium sweeteners as well as TES, specific differences exist and provide guidance for the design of new artificial sweeteners. In case of the nonsweetener TES, the interactions with the receptor are indirectly mediated through a hydrogen bonded water network, while the sweeteners bind with high affinity directly to the receptor. The presence of a hydrophobic group interacting with multiple receptor residues as a major determinant for sweet taste has been confirmed. The nature of the hydrophobic group is likely a discriminator for super-versus high-potency sweeteners, which can be exploited in the design of new, highly potent sweetener compounds. Overall similarities and partial conservation of interactions indicate that the NC6.8 Fab surrogate is representing crucial features of the T1R2 taste receptor VFTM binding site.
机译:已经确定了与高效甜味剂化合物SC45647和不变味的高亲和力拮抗剂TES复合的鼠单克隆IgG2b(kappa)抗体NC6.8 Fab片段的晶体结构。晶体结构表明如何通过特定受体残基与功能不同的甜味剂基团之间的多次相互作用来微调甜味剂的效力。与超高效甜味剂NC174配合的NC6.8结构的比较分析表明,尽管NC6.8抗原结合袋中的相同残基与两性离子三取代胍盐甜味剂和TES相互作用,但存在特定差异并提供新型人工甜味剂设计指南。在使用非甜味剂TES的情况下,与受体的相互作用是通过氢键水网络间接介导的,而甜味剂则以高亲和力直接与受体结合。已经证实与多个受体残基相互作用的疏水基团的存在是甜味的主要决定因素。疏水基团的性质可能是超强效甜味剂的区分因素,可以在设计新型高效甜味剂化合物时加以利用。总体相似性和相互作用的部分保守性表明,NC6.8 Fab替代物代表T1R2味觉受体VFTM结合位点的关键特征。

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