The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain.
The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain.
复制标题
DOI：
10.1038/nsmb.2340
复制
发表时间：
2012-08
影响因子：
16.8
通讯作者：
Naismith, James H.
中科院分区：
文献类型：
--
作者：
Koehnke, Jesko;Bent, Andrew;Houssen, Wael E.;Zollman, David;Morawitz, Falk;Shirran, Sally;Vendome, Jeremie;Nneoyiegbe, Ada F.;Trembleau, Laurent;Botting, Catherine H.;Smith, Margaret C. M.;Jaspars, Marcel;Naismith, James H.
肽大环化合物存在于许多具有生物活性的天然产物中。它们的多功能性、抗蛋白水解性和穿过膜的能力使它们成为理想的分子。虽然存在合成此类化合物的技术，但天然大环化合物中发现的多样性的全部程度尚未通过合成实现。蓝藻毒素是核糖体肽大环化合物，包含非常多样化的环大小，氨基酸和化学修饰。我们报告的结构，生化特性和初始工程的PatG大环化酶结构域的Prochloron sp.从patellamide途径，催化大环化的线性肽。该酶在枯草杆菌蛋白酶折叠中含有插入物，使其能够识别三个残基的签名，以预先组织的和不寻常的构象结合底物，保护酰基酶中间体免受水的影响并催化肽键形成。大环化大范围的非活化底物的能力具有广泛的生物技术应用。
Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acyl-enzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications.
登录
查看更多内容
影响因子：
14.8
作者：
Donia, Mohamed S.;Hathaway, Brian J.;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.
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：
12.8
作者：
Ahvazi, B;Steinert, PM
通讯作者：
Steinert, PM
影响因子：
11.9
作者：
McIntosh JA;Donia MS;Schmidt EW
通讯作者：
Schmidt EW
影响因子：
14.8
作者：
Donia, Mohamed S.;Ravel, Jacques;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.