10月5日,，J. Biol. Chem.在線發(fā)表了生化與細胞所王恩多研究組研究論文：血紅素結合人細胞質精氨酰-tRNA合成酶并抑制其催化活力。

人細胞質精氨酰-tRNA合成酶(hcArgRS)催化tRNAArg氨基?；葾rg-tRNAArg,。Arg-tRNAArg一方面是蛋白質生物合成的原料，參與蛋白質合成,；另一方面它也是精氨酰-tRNA：蛋白質轉移酶的底物,，轉移精氨酰基到蛋白質的N-末端,，參與依賴泛素化的“N-末端規(guī)則”蛋白質降解途徑,。哺乳動物細胞的ArgRS即參與蛋白質生物合成，又參與蛋白質的降解,，如何調節(jié)ArgRS的這兩個相反的功能是非常重要的科學問題,。血紅素作為信號分子，參與到許多重要的生命活動中,，其中“N-末端規(guī)則”途徑就是一個血紅素的感應器,。

王恩多實驗室的楊芳博士研究了血紅素與hcArgRS在體外的相互作用，研究結果表明血紅素能夠以hcArgRS的Cys-115 作為特異性的軸向配體與之結合,，血紅素通過抑制hcArgRS的第一步反應—氨基酸活化反應,，而抑制酶的tRNA精氨酰化活力,。血紅素誘導hcArgRS的寡聚化是其抑制該酶催化活力的主要原因,。氨基酰-tRNA合成酶家族是一個功能多樣的蛋白質家族，該研究對進一步深入探索哺乳動物ArgRS新的生物學功能提供了極有價值的線索,。

該研究工作得到科技部重大科學研究計劃,，中國博士后基金，上海市博士后基金,，中科院王寬誠博士后基金以及上海生科院博士后基金的經費資助,。(生物谷Bioon.com)

生物谷推薦英文摘要：

JBC doi: 10.1074/jbc.M110.159913

Hemin binds to human cytoplasmic arginyl-tRNA synthetase and inhibits its catalytic activity
Fang Yang, Xian Xia, Hui-Yan Lei and En-Duo Wang*

The free form of human cytoplasmic arginyl-tRNA synthetase (hcArgRS) is hypothesized to participate in ubiquitin-dependent protein degradation by offering arginyl-tRNAArg to arginyl-tRNA transferase (ATE1). We investigated the effect of hemin on hcArgRS based on the fact that hemin regulates several critical proteins in "N-end rule"protein degradation pathway. Extensive biochemical evidence has established that hemin could bind to both forms of hcArgRS in vitro. Based on the spectral changes of the Soret band on site-directed protein mutants, we identified Cys-115 as a specific axial ligand of hemin binding that is located in the Add1 domain. Hemin inhibited the catalytic activity of full-length and N-terminal 72-amino acid truncated hcArgRSs by blocking amino acid activation. Kinetic analysis demonstrated that the Km values for tRNAArg, arginine and ATP in the presence of hemin were not altered, but kcat values dramatically decreased compared with those in the absence of hemin. By comparison, the activity of prokaryotic ArgRS was not affected obviously by hemin. Gel filtration chromatography suggested that hemin induced oligomerization of both the isolated Add1 domain and the wild type enzyme, which could account for the inhibition of catalytic activity. However, the catalytic activity of a hcArgRS mutant with Cys-115 replaced by alanine (hcArgRS-C115A) was also inhibited by hemin, suggesting that hemin binding to Cys-115 is not responsible for the inhibition of enzymatic activity and that the specific binding may participate in other biological functions.