finally, 爷 oral defense 了

> CR2,SBS,NTU,2:30pm,3 Dec,2009.

欢迎捧场！

 

The NS3 Protein from Dengue Virus: Structure and Function

 

Dahai Luo

 

 

Abstract

The non-structural protein 3 (NS3) from dengue virus is a multifunctional protein of 69 kDa. The N terminal domain of NS3 is a serine protease with NS2B as a cofactor essential for viral polyprotein processing. The C terminal domain is a RNA helicase and a nucleoside 5’ triphosphatase, involved in viral replication and virus particle assembly. Thus, NS3 plays an important role in viral life cycle and represents a target for the development of specific antiviral inhibitors.

A complete NS3 molecule fused with 18 residues of the NS2B cofactor through a flexible linker (scNS2B₁₈NS3) was engineered. The first crystal structure of scNS2B₁₈NS3 was determined as apo enzyme to 3.1 Å. The relative orientation between the protease and helicase domains is drastically different compared to the scNS3-NS4A molecule from hepatitis C virus (HCV). A second conformation of scNS2B₁₈NS3 was also discovered, in which the protease domain rotates ~ 161° relative to the helicase domain in contrast to that in Conformation I. The structural dynamics of scNS2B₁₈NS3 and the potential impacts to the enzymatic activities as well as its roles in viral life cycle are discussed.

Together with the NS5 polymerase, the NS3 helicase plays a pivotal role in flavivirus RNA replication. The dengue virus NS3 helicase was captured at several stages along the catalytic pathway: ligand-free state, bound to single stranded RNA, to an ATP analog, to a Vanadate-trapped ADP complex and to ATP hydrolysis products. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule for ATP hydrolysis and point to a b-hairpin that protrudes from subdomain 2 as a critical element for dsRNA unwinding. They also suggest how NS3 could act as an RNA anchoring device and thus participate both in flavivirus RNA replication and assembly.

 

 

皆有可能，算不得什么。。。

 

 

难道只有古道西风瘦马才配的上唐吉诃德么

 

 

去河内过年？

11月5日，第14届三星保险杯半决赛决赛在上海韩国文化院战罢，邱峻八段执白中盘击败李昌镐九段，三番棋2比1胜出，与孔杰成功会师决赛。

中国棋手邱峻本届三星杯表现神勇，本赛中先后力克韩国名将宋泰坤和许映皓，首次闯入世界大赛四强。半决赛中，面对韩国天王李昌镐，邱峻以近乎完美的表现在首局中完胜对手，占得先机，遗憾的是在次局的较量中，“石佛”李昌镐在最后关头抓住邱峻的一次误算奋勇屠龙，顽强扳回一局，将半决赛拖入决胜局。经过再次猜先，决胜局由李昌镐执黑先行，布局未几双方便在左下角展开激战，执白的邱峻行棋顺畅，潜入白阵的黑棋则陷入苦战，弈至中午封盘，白棋形势占优。进入中后盘两人轮流长考，面对复杂局势都不敢轻举妄动，在左上角形成转换后，白棋实空领先，局面进入收官阶段。最后关头，李昌镐奋力追赶，但终无力挽回局面，至第228手停钟认负，无缘决赛。

偶像老去了。。。

 

 

后记：偶像赢了不好，输了也不好。

别人的输赢看得都揪心，何况自己的呢？还要好好修炼哪。。。

 

 

六月正式写完并交上去；

发现七月二十多才到graduatoffic；

中间不知道被谁稀罕了一个月；

三个月的时间被他们充分的用过去；

十月十号才回来；

我二十号再交上去；

我改什么了？你再看一个月？

他们说十一月中旬才能回来；

然后，

oral defens；

再审再议；

再议再审；

。。。

圣诞节前是肯定够呛了。

 

就这个拖拉机，还搞什么mit havad。好学生不是拖出来的。平时也没个什么委员会的帮着参谋监督，到最后无关宏旨的地方墨迹拖拉没完。原本师生质量就差，学生都没脑袋的乱撞，导师都席了糊涂的胡导。

整天学整天仿，好东西一点没学来，多少新娘都熬成婆娘了。。。