Acetohydroxyacid synthase(AHAS) is the target enzyme of several classes of herbicides,such as sulfonylureas and imidazolinones.Now many mutant AHASs with herbicide resistance have emerged along with extensive use of herbicides,therefore it is imperative to understand the detailed interaction mechanism and resistance mechanism so as to develop new potent inhibitors for wild-type or resistant AHAS.With the aid of available crystal structures of the Arabidopsis thaliana(At) AHAS-inhibitor complex,molecular dynamics(MD) simulations were used to investigate the interaction and resistance mechanism directly and dynamically at the atomic level.Nanosecond-level MD simulations were performed on six systems consisting of wild-type or W574L mutant AtAHAS in the complex with three sulfonylurea inhibitors,separately,and binding free energy was calculated for each system using the MM-GBSA method.Comprehensive analyses from structural and energetic aspects confirmed the importance of residue W574,and also indicated that W574L mutation might alert the structural charactersistic of the substrate access channel and decrease the binding affinity of inhibitors,which cooperatively weaken the effective channel-blocked effect and finally result in weaker inhibitory effect of inhibitor and corresponding herbicide resistance of W574L mutant.To our knowledge,it is the first report about MD simulations study on the AHAS-related system,which will pave the way to study the interactions between herbicides and wild-type or mutant AHAS dynamically,and decipher the resistance mechanism at the atomic level for better designing new potent anti-resistance herbicides.
YU ZhiHong,WEN Xin & XI Zhen State Key Laboratory of Elemento-Organic Chemistry
A series of Olaparib derivatives was synthesized, and their structures were confirmed by 1H NMR, MS and elemental analysis. Their antitumor activities on breast cancer susceptbility gene 1/2（BRCAl/2）-deficient cancer cell lines including HCC1937, Capan-1 and MDA-MB-436 were evaluated. The antitumor activity of compound Olaparib-1 was better than the positive control Olaparib in BRCAl-deficient cell line HCC1937.
Acetohydroxyacid synthase(AHAS,EC 2.2.1.6) is a key enzyme in branched-chain amino acid metabolism in plants,f...
NIU CongWei~*,SUN Lu,WEN Xin,FENG Wei,XI Zhen State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, Nankai University,Tian jin 300071,China
＜正＞Tobacco mosaic virus（TMV） is known to infect more than 150 types of herbaceous, dicotyledonous plants inclu...
Shuang Gao,Xin Wen,Congwei Niu,Zhen Xi~* State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology,Nankai University,Tianjin,300071,China
Homologous and heterologous interactions between acetohydroxyacid synthase (AHAS) I and Ⅲ from E. coli have been studied by surface plasmon resonance (SPR). The catalytic and regulatory subunits association for AHAS I (KD = 1.13 × 10-7 M) was stronger than that for AHAS Ⅲ (KD = 5.29 × 10-7 M). A strong heterologous association between regulatory and catalytic subunits and heterologous activation of catalytic subunits were observed. SPR results combined with enzyme kinetics indicate that the reconstituted heterologous enzymes had similar kinetic properties as homologous enzymes, implying that the regulatory subunit of AHAS I could be replaced by the regulatory subunit of AHAS Ⅲ and vice versa. This work may be useful to further understandings of the mechanism of regulation of AHAS.
NIU CongWei, FENG Wei, ZHOU YanFei, WEN Xin & XI Zhen State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, Nankai University, Tianjin 300071, China
