5 ' -methylthioadenosine Femtomolar过渡态类似物抑制剂/ S-adenosylhomocysteine核苷酶大肠杆菌。
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辛格V,埃文斯GB,楞次DH,梅森JM,赢得K,梅伊,画家GF,泰勒PC,福尔诺RH忙于打捞收拾悉尼湾号,李我,豪厄尔PL,施拉姆六世
5 ' -methylthioadenosine Femtomolar过渡态类似物抑制剂/ S-adenosylhomocysteine核苷酶大肠杆菌。
生物化学杂志。2005年5月6日,280 (18):18265 - 73。Epub 2005年3月4。
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15749708 (在PubMed]
- 文摘
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大肠杆菌5 ' -methylthioadenosine / S-adenosyl-homocysteine核苷酶(MTAN)水解底物形成腺嘌呤和5-methylthioribose(地铁)或S-ribosylhomocysteine (SRH)。5 ' -Methylthioadenosine (MTA)是聚胺合成的副产品和SRH生物合成的前体是一个或多个群体感应autoinducer分子。MTAN因此参与群体感应,回收MTA的聚胺通路通过腺嘌呤phosphoribosyltransferase和回收地铁蛋氨酸。水解MTA的大肠杆菌MTAN涉及高度与ribooxacarbenium离子离解过渡态的性格。Iminoribitol MTA的模拟过渡态的MTAN合成抑制剂和测试。5 ' -Methylthio-Immucillin-A (MT-ImmA)是一种起病缓慢紧束缚抑制剂给离解常数(K(我)(*))77点。替换methylthio组与p-Cl-phenylthio组给了一个更强大的抑制剂的离解常数2点。大肠杆菌MTAN DADMe-Immucillins抑制剂更好,因为他们更密切相关的高度离解特性过渡状态。MT-DADMe-Immucillin-A结合K(我)(*)下午2点的价值。更换5 '甲基组与其他疏水组给17过渡态类似物抑制剂与离解常数从10(-12)到10 (-14)m。最强大的抑制剂是5 ' -p-Cl-phenylthio-DADMe-Immucillin-A (pClPhT-DADMe-ImmA), K (i)(*)的价值47调频(47 x 10(-15)米)。这些都是最强大的非共价酶抑制剂报道,绑定9 - 91倍收紧MTA SAH基质,分别。 The inhibitory potential of these transition state analogue inhibitors supports a transition state structure closely resembling a fully dissociated ribooxacarbenium ion. Powerful inhibitors of MTAN are candidates to disrupt key bacterial pathways including methylation, polyamine synthesis, methionine salvage, and quorum sensing. The accompanying article reports crystal structures of MTAN with these analogues.