朱德煦
主要研究方向为用蛋白质工程手段研究蛋白质(酶)结构和功能的关系。
个性化签名
- 姓名:朱德煦
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师,
- 职称:-
-
学科领域:
光学
- 研究兴趣:主要研究方向为用蛋白质工程手段研究蛋白质(酶)结构和功能的关系。
1931年12月出生,1958-1961年南京大学生化专业研究生,曾任南京大学生化系主任,南京大学医药生物技术国家重点实验室主任,南京大学生命科学院院长,国家高技术发展计划生物技术领域专家委员会委员。1979-1982为美国威斯康星大学生化系高级科学家,专长为生物化学和分子生物学,主要研究方向为用蛋白质工程手段研究蛋白质(酶)结构和功能的关系。曾主持3项国家863高技术项目,一项国家攀登计划子项目及多项国家自然科学基金项目,发表研究论文120余篇2次获国家科学技术进步奖,在人重组尿激酶素结构和功能间关系的研究获2000年国家自然科学二等奖,为第一完成人。2004年5月因抗幽门螺旋杆菌的新化合物获美国发明专利。
-
主页访问
2474
-
关注数
0
-
成果阅读
416
-
成果数
8
朱德煦
,-0001,():
-1年11月30日
-
58浏览
-
0点赞
-
0收藏
-
0分享
-
102下载
-
0评论
-
引用
【期刊论文】Renaturation of Recombinant Human Pro-Urokinase Expressed in Escherichia coli
朱德煦
,-0001,():
-1年11月30日
-
54浏览
-
0点赞
-
0收藏
-
0分享
-
166下载
-
0评论
-
引用
朱德煦
,-0001,():
-1年11月30日
-
52浏览
-
0点赞
-
0收藏
-
0分享
-
112下载
-
0评论
-
引用
朱德煦
,-0001,():
-1年11月30日
-
53浏览
-
0点赞
-
0收藏
-
0分享
-
101下载
-
0评论
-
引用
朱德煦, Ziyong Sun, ‡, § Bei-Fang Liu, ‡ Yuhong Chen, ‡ Victor Gurewich, § Dexu Zhu, ‡ and Jian-Ning Liu*, §
Biochemistry 1998, 37, 2935-2940,-0001,():
-1年11月30日
It was recently proposed that hydrophobic interactions control the active conformation of serine proteases in the trypsin family (Hedstrom et al. (1996) Biochemistry 35, 4515-23) rather than a charge interaction with Asp next to the active site Ser, as formerly believed. In the present study, certain sitedirected mutants of the serine protease zymogen pro-urokinase (pro-UK) and its two-chain enzymatic derivative urokinase (UK) were characterized. The results provide information on the structure-function of the catalytic domain of pro-UK/UK, which is relevant to this controversy. Mutations at Asp355(c194), which eliminated its charge, induced a 6250-fold reduction in the catalytic activity of UK. By contrast, reducing the hydrophobicity at the neoterminal Ile159(c16) of UK had relatively little effect. However, when both the hydrophobicity and the size of the side chain were reduced by a glycine substitution at this position, a major reduction (9090-fold) in the catalytic efficiency of UK occurred. This effect was related to the smaller side chain increasing the cavity and the flexibility of the N-terminus and thereby interfering with its charge interaction with Asp355(c194). A similar mechanism, rather than a change in hydrophobicity, is believed also to explain the reduction in the stabilization energy of the activation domain observed in a trypsin mutant by Hedstrom et al. (1996). Although hydrophobic interaction facilitated the charge interaction with Asp355(c194), the latter was the primary force which stabilized the active conformation of UK. The charge interaction with Asp355(c194) was also found to be the principal determinant of the intrinsic catalytic activity of single-chain pro-UK. Additionally, the findings confirmed that the KM of pro-UK for its natural substrate was significantly lower than that of UK. Since this same phenomenon was also seen with each of the mutants, the substrate binding pocket of these single-chain zymogens was better formed than that of their two-chain, enzymatic derivatives.
-
50浏览
-
0点赞
-
0收藏
-
0分享
-
142下载
-
0评论
-
引用
【期刊论文】a-Lactalbumin Mutant Acting as Lysozyme
朱德煦, Yuming Xue, Jian-Ning Liu, , Ziyong Sun, Zhong Ma, Chunlei Wu, and Dexu Zhu* State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, People's Republic of China; Institute of Molecular Medicine, People's Republic of China
PROTEINS: Structure, Function, and Genetics 42: 17-22 (2001),-0001,():
-1年11月30日
A mutant of a-lactalbumin was expressed and purified, in which His32, Thr33, Glu49, Ile59, Val99, and Tyr103 were substituted by Leu32, Glu33, Asp49, Trp59, Asn99, and Ala103, respectively, to create a catalytic site of lysozyme in a-lactalbumin. The mutant catalyzed hydrolysis of the synthetic substrate, pNP-(NAcGlc)3, with a KM and kcat of 0.160
a-lactalbumin, chicken lysozyme, chitopentaose, glycosidic bond, isothermal titration calorimeter, pNP-(, NAcGlc), 3
-
53浏览
-
0点赞
-
0收藏
-
0分享
-
149下载
-
0评论
-
引用
朱德煦, Ziyong Sun‡§, Yongping Jiang‡, Zong Ma§, Hui Wu‡, Bei-Fang Liu§, Yuming Xu§, Wei Tang‡, Yuhong Chen§, Cuizhen Li‡, Dexu Zhu§, Victor Gurewich‡, and Jian-Ning Liu‡§¶
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 272, No.38, Issue of September 19, pp. 23818-23823, 1997,-0001,():
-1年11月30日
Pro-urokinase has a much higher intrinsic catalytic activity than other zymogens of the serine protease family. Lys300(c143) in an apparent "flexible loop" region (297-313) was previously shown to be an important determinant of this intrinsic catalytic activity. This was related to the loop allowing the positive charge of Lys300(c143) to transiently interact with Asp355(c194), thereby inducing an active conformation of the protease domain (Liu, J. N., Tang, W., Sun, Z., Kung, W., Pannell, R., Sarmientos, P., and Gurewich, V. (1996) Biochemistry 35, 14070-14076). To further test this hypothesis, the charge at position 300(c143) and the flexibility of the loop were altered using site-directed mutagenesis designed according to a computer model to affect the interaction between Lys300(c143) and Asp355(c194). When the charge at Lys300(c143) but not Lys313(c156) was reduced, a significant reduction in the intrinsic catalytic activity occurred. Similarly, when the flexibility (wobbliness) of the loop was enhanced reducing the size of side chain, the intrinsic catalytic activity was also reduced. By contrast, when the loop was made less flexible, the intrinsic catalytic activity was increased. These findings were consistent with the hypothesis. The effects of these mutations on two-chain activity were less and often discordant with the intrinsic catalytic activity, indicating that they can be modulated independently. This structure-function disparity can be exploited to create a more zymogenic pro-urokinase (lower intrinsic catalytic activity) with a high catalytic activity, as exemplified by two of the mutants. The changes in intrinsic catalytic activity and two-chain activity induced by the mutations were due to changes in kcat rather than Km. Some significant structure-function differences between prourokinase and its highly homologous counterpart, tissue plasminogen activator, were also found.
-
39浏览
-
0点赞
-
0收藏
-
0分享
-
106下载
-
0评论
-
引用
朱德煦, Ni Cheng, a Jian-Shu Xie, b Min-Yue Zhang, a Chang Shua and De-Xu Zhua, *
Bioorganic & Medicinal Chemistry Letters 13(2003)2703-2707,-0001,():
-1年11月30日
The synthesis and anti-Helicobacter pylori activity of a novel agent NE2001, 4-(4-methylbenzyl)-40-[guanidinomethylbenzoyloxy] biphenyl-4-carboxylate hydrochloride, are described. NE2001 had a specific inhibitory effect on the growth of H. pylori preceded by the suppression DNA synthesis in the cell. The effects of NE2001 on RNA and protein syntheses in H. pylori were also examined.
-
57浏览
-
0点赞
-
0收藏
-
0分享
-
114下载
-
0评论
-
引用