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首页> 外文期刊>The FEBS journal >Solution structure of hirsutellin A - new insights into the active site and interacting interfaces of ribotoxins
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Solution structure of hirsutellin A - new insights into the active site and interacting interfaces of ribotoxins

机译：hirsutellin A的溶液结构-核糖毒素活性位点和相互作用界面的新见解

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Hirsutellin (HtA) is intermediate in size between other ribotoxins and less specific microbial RNases, and thus offers a unique chance to determine the minimal structural requirements for activities unique to ribotoxins. Here, we have determined the structure of HtA by NMR methods. The structure consists of one l-helix, a helical turn and seven o-strands that form an N-terminal hairpin and an anti-parallel o-sheet, with a characteristic l + o fold and a highly positive charged surface. Compared to its larger homolog l-sarcin, the N-terminal hairpin is shorter and less positively charged. The secondary structure elements are connected by large loops with root mean square deviation (rmsd) values > 1 c, suggesting some degree of intrinsically dynamic behavior. The active site architecture of HtA is unique among ribotoxins. Compared to l-sarcin, HtA has an aspartate group, D40, replacing a tyrosine, and the aromatic ring of F126, located in the leucine 'environment' close to the catalytic H113 in a similar arrangement to that found in RNase T1. This unique active site structure is discussed in terms of its novel electrostatic interactions to understand the efficient cytotoxic activity of HtA. The contributions of the N-terminal hairpin, loop 2 and loop 5 with regard to protein functionality, protein-protein and protein-lipid interactions, are also discussed. The truncation and reduced charge of the N-terminal hairpin in HtA may be compensated for by the extension and new orientation of its loop 5. This novel orientation of loop 5 re-establishes a positive charge on the side of the molecule that has been shown to be important for intermolecular interactions in ribotoxins.
机译：Hirsutellin（HtA）的大小介于其他核糖毒素和特异性较低的微生物RNase之间，因此为确定核糖毒素独特活性的最低结构要求提供了独特的机会。在这里，我们已经通过NMR方法确定了HtA的结构。该结构由一个l螺旋，一个螺旋形匝和7条o链组成，这些o链形成一个N末端发夹和一个反平行的o型折叠，具有特征性的l + o折叠和高度带正电的表面。与其较大的同系物l-sarcin相比，其N末端发夹更短且带正电荷的较少。二级结构元素通过大环路连接，均方根偏差（rmsd）值> 1 c，表明存在某种程度的内在动力学行为。在核糖毒素中，HtA的活性位点结构是独特的。与l-sarcin相比，HtA具有天冬氨酸基团D40（取代酪氨酸），F126的芳环位于亮氨酸“环境”中，靠近催化H113，其排列方式与RNase T1类似。根据其新颖的静电相互作用来讨论这种独特的活性位点结构，以了解HtA的有效细胞毒活性。还讨论了N末端发夹，环2和环5在蛋白质功能，蛋白质-蛋白质和蛋白质-脂质相互作用方面的作用。 HtA中N末端发夹的截短和减少的电荷可以通过其环5的延伸和新方向来补偿。环5的这种新方向在已显示的分子侧重新建立了正电荷对核毒素中的分子间相互作用很重要。

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