Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin
Common binding site for disialyllactose and tri-peptide in C-fragment of tetanus neurotoxin
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DOI：
10.1002/prot.20595
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发表时间：
2005-11-01
影响因子：
2.9
通讯作者：
Swaminathan, S
中科院分区：
文献类型：
--
作者：
Jayaraman, S;Eswaramoorthy, S;Swaminathan, S
梭菌神经毒素由肉毒杆菌（BoNT）和破伤风（TeNT）组成，它们具有显著的结构和功能相似性。与二唾液酸乳糖（DiSia）和三肽Tyr-Glu-Trp（YEW）复合的TeNT结合结构域的晶体结构已被确定为分别为2.3和2.2埃。DiSia和YEW都结合在β-三叶结构域分子表面的浅裂区域，与一组常见的残基Asp 1147、Asp 1214、Asn 1216和Arg 1226相互作用。DiSia和YEW在破伤风毒素中的相同位点结合提供了可以被神经节苷脂部分或肽占据的推定位点。用YEW和DiSia的混合物进行的浸泡实验表明，YEW与DiSia竞争，表明YEW可用于阻断神经节苷脂结合。与TeNT结合结构域与小分子复合物BoNT/A和/B的比较提供了对神经节苷脂结合的不同模式的洞察。
Clostridial neurotoxins are comprised of botulinum (BoNT) and tetanus (TeNT), which share significant structural and functional similarity. Crystal structures of the binding domain of TeNT complexed with disialyllactose (DiSia) and a tri-peptide Tyr-Glu-Trp (YEW) have been determined to 2.3 and 2.2 angstrom, respectively. Both DiSia and YEW bind in a shallow cleft region on the surface of the molecule in the beta-trefoil domain, interacting with a set of common residues, Asp1147, Asp1214, Asn1216, and Arg1226. DiSia and YEW binding at the same site in tetanus toxin provides a putative site that could be occupied either by a ganglioside moiety or a peptide. Soaking experiments with a mixture of YEW and DiSia show that YEW competes with DiSia, suggesting that YEW can be used to block ganglioside binding. A comparison with the TeNT binding domain in complex with small molecules, BoNT/A and /B, provides insight into the different modes of ganglioside binding.