A conformationally restricted uniconazole analogue as a specific inhibitor of rice ent-kaurene oxidase CYP701A6
A conformationally restricted uniconazole analogue as a specific inhibitor of rice ent-kaurene oxidase CYP701A6
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构象限制的烯效唑类似物作为水稻贝壳杉烯氧化酶 CYP701A6 的特异性抑制剂
DOI：
10.1016/j.bmcl.2012.03.028
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
N
中科院分区：
文献类型：
--
作者：
Todoroki;Y.; Naiki;K.; Muramatsu;T.; Ohnishi;T.; Ueno;K.;Mizutani;M.; Hirai;N
植物生长延缓剂烯效唑（uniconazole，UNI）是赤霉素生物合成中的内贝壳杉烯氧化酶（ent-kaurene oxidase，CYP 701 A）的有效抑制剂，同时也对脱落酸催化剂中的关键酶阿坝8′-羟化酶（abscisic acid catenase，CYP 707 A）具有强烈的抑制作用。唑类P450抑制剂通过sp2氮与血红素铁原子配位并通过亲脂区域与周围蛋白质残基相互作用而与P450活性位点结合。我们推测，UNI的选择性差可能是由于其小分子尺寸和灵活的构象，使其能够适应不同大小和形状的活性位点。为了找到一个选择性抑制剂的CYP 701 A基于这一假设，我们研究了抑制活性的三种类型的UNI类似物，这是构象约束，扩大的宽度，扩大的长度，对重组水稻CYP 701 A6和拟南芥CYP 707 A3。构象限制性类似物UFAP 2和UFAP 2N对CYP 701 A6的抑制作用与UNI一样强，而对CYP 707 A3的抑制作用低于UNI。
The plant growth retardant uniconazole (UNI), which has been used as an effective inhibitor of ent-kaurene oxidase (CYP701A) involved in gibberellin biosynthesis, also strongly inhibits ABA 8′-hydroxylase (CYP707A), a key enzyme in abscisic acid catabolism. Azole P450 inhibitors bind to the P450 active site by both coordinating to the heme-iron atom via an sp2nitrogen and interacting with surrounding protein residues through a lipophilic region. We hypothesized that poor selectivity of UNI may result from its small molecular size and flexible conformation that allows it to fit into active sites differing in size and shape. To find a selective inhibitor of CYP701A based on this hypothesis, we examined inhibitory activities of three types of UNI analogues, which were conformationally constrained, enlarged in width, and enlarged in length, against recombinant rice CYP701A6 and Arabidopsis CYP707A3. Conformationally restricted analogues, UFAP2 and UFAP2N, inhibited CYP701A6 as strongly as UNI, whereas it inhibited CYP707A3 less than UNI.