Inhibitory effect of a self-derived peptide on glucosyltransferase of Streptococcus mutans -: Possible novel anticaries measures
Inhibitory effect of a self-derived peptide on glucosyltransferase of Streptococcus mutans -: Possible novel anticaries measures
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DOI：
10.1074/jbc.274.22.15797
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发表时间：
1999-05-28
影响因子：
4.8
通讯作者：
Hanada, N
中科院分区：
文献类型：
--
作者：
Eto, A;Saido, TC;Hanada, N
葡萄糖转移酶(GTF)在龋病的发生发展中起着重要作用。我们检查了酶分子中可能存在的自我抑制片段，目的是通过抑制GTF来开发防龋措施。研究了来自不同区域的22个合成肽对催化活性的影响，这些合成肽可能与不溶性葡聚糖的合成有关。其中1个氨基酸序列与1176-1194氨基酸序列相同，对GTF-I显著和特异地抑制蔗糖水解酶和葡糖转移为葡聚糖，双互易分析表明该抑制作用是非竞争性的。随机序列相同氨基酸组成的杂乱肽对GTF-I活性无影响。此外，即使在十二烷基硫酸钠(十二烷基硫酸钠)存在的情况下，一旦络合，多肽也会与酶紧密结合。利用光学消逝共振镜试管系统进行的动力学分析表明，酶-多肽相互作用是两相的。这些结果表明，该肽以高亲和力直接与酶相互作用，并以序列特异性的方式抑制其活性。这种多肽本身可能是一种有效的防龋剂，尽管其有效性可以通过进一步的修饰来提高。
Glucosyltransferase (GTF) plays an important role in the development of dental caries. We examined the possible presence of self-inhibitory segments within the enzyme molecule for the purpose of developing anticaries measures through GTF inhibition. Twenty-two synthetic peptides derived from various regions presumably responsible for insoluble-glucan synthesis were studied with respect to their effects on catalytic activity. One of them, which is identical in amino acid sequence to residues 1176-1194, significantly and specifically inhibited both sucrose hydrolysis and glucosyl transfer to glucan by GTF-I, Double-reciprocal analysis revealed that the inhibition is noncompetitive. Scramble peptides, composed of the identical amino acids in randomized sequence, had no effect on GTF-I activity. Furthermore, the peptide is tightly bound to the enzyme once complexed, even in the presence of sodium dodecyl sulfate (SDS). Kinetic analysis using an optical evanescent resonant mirror cuvette system demonstrated that the enzyme-peptide interaction was biphasic. These results indicate that the peptide directly interacts with the enzyme with high affinity and inhibits its activity in a sequence-specific manner. This peptide itself could possibly be an effective agent for prevention of dental caries, although its effectiveness may be improved by further modification.