Oxidation of the Cyanobactin Precursor Peptide Is Independent of the Leader Peptide and Operates in a Defined Order.
Oxidation of the Cyanobactin Precursor Peptide Is Independent of the Leader Peptide and Operates in a Defined Order.
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DOI：
10.1021/acs.biochem.8b00835
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发表时间：
2018-10-16
期刊：
影响因子：
2.9
通讯作者：
Naismith JH
中科院分区：
文献类型：
--
作者：
Gao S;Ge Y;Bent AF;Schwarz-Linek U;Naismith JH
五元氮加杂原子环被称为唑啉或氧化形式的唑，在天然产物和药物中非常常见。蓝菌素类天然产物中噻唑啉氧化为噻唑是已知可改变化合物生物特性的几个重要转化之一。蓝菌素生物合成过程中发生的各种化学反应的顺序尚不完全清楚。负责氧化多种噻唑啉的黄素依赖性酶的结构表明，它包含一个在其他酶中识别线性肽的附加结构域。我们表征了酶在两种底物上的活性：一种具有肽前导序列，另一种不具有。动力学和生物物理学表明底物上的前导序列不被酶识别。在体外，该酶对任一底物的作用速度都比大环化酶或蛋白酶更快。该酶对同一线性肽中的多个噻唑啉具有优选的氧化顺序。
The five-membered nitrogen plus heteroatom rings known as azolines or in their oxidized form as azoles are very common in natural products and drugs. The oxidation of thiazoline to thiazole in the cyanobactin class of natural products is one of the several important transformations that are known to alter the biological properties of the compound. The ordering of the various chemical reactions that occur during cyanobactin biosynthesis is not fully understood. The structure of the flavin-dependent enzyme responsible for the oxidation of multiple thiazolines reveals it contains an additional domain that in other enzymes recognizes linear peptides. We characterize the activity of the enzyme on two substrates: one with a peptide leader and one without. Kinetics and biophysics reveal that the leader on the substrate is not recognized by the enzyme. The enzyme is faster on either substrate than the macrocyclase or protease in vitro. The enzyme has a preferred order of oxidation of multiple thiazolines in the same linear peptide.
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DOI：
10.1073/pnas.1703663114
发表时间：
2017-09-26
影响因子：
11.1
作者：
Davis, Katherine M.;Schramma, Kelsey R.;Ando, Nozomi
通讯作者：
Ando, Nozomi
影响因子：
16.6
作者：
Houssen, Wael E.;Bent, Andrew F.;McEwan, Andrew R.;Pieiller, Nathalie;Tabudravu, Jioji;Koehnke, Jesko;Mann, Greg;Adaba, Rosemary I.;Thomas, Louise;Hawas, Usama W.;Liu, Huanting;Schwarz-Linek, Ulrich;Smith, Margaret C. M.;Naismith, James H.;Jaspars, Marcel
通讯作者：
Jaspars, Marcel
影响因子：
14.8
作者：
Koehnke J;Mann G;Bent AF;Ludewig H;Shirran S;Botting C;Lebl T;Houssen W;Jaspars M;Naismith JH
通讯作者：
Naismith JH
影响因子：
15
作者：
McIntosh, John A.;Robertson, Charles R.;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.
影响因子：
7.8
作者：
Czekster, Clarissa Melo;Ge, Ying;Naismith, James H.
通讯作者：
Naismith, James H.