Structure-Activity Relationships for Thyroid Hormone Deiodination by Mammalian Type I Iodothyronine Deiodinases1.
Structure-Activity Relationships for Thyroid Hormone Deiodination by Mammalian Type I Iodothyronine Deiodinases1.
复制标题
哺乳动物 I 型碘甲状腺原氨酸脱碘酶对甲状腺激素脱碘的结构-活性关系1。
作者：
N. Toyoda;E. Kaptein;M. Berry;J. Harney;P. R. Larsen;T. Visser;Thyroid Division
甲状腺激素的生物活性在很大程度上由肝硒酶I型碘甲状腺原氨酸脱碘酶（ID 1）对激素原T4的单脱碘作用决定，即通过外环脱碘（ORD）形成活性激素T3，或通过内环脱碘（IRD）形成无活性代谢物rT 3。ID 1还催化T3的IRD和rT 3的ORD转化为T2，以及不同的碘甲腺原氨酸硫酸盐的脱碘，例如T3 S的IRD和T2 S的ORD。先前的研究表明，狗ID 1（dID 1）和人ID 1（hID 1）之间的催化特异性存在重要差异，特别是在rT 3的ORD方面。本研究通过比较肝微粒体中天然dID 1和hID 1以及HEK 293细胞中表达的重组野生型、嵌合型和突变型d/hID 1酶对T4、T3、rT 3、T3 S和T2 S的脱碘作用，研究该酶的结构和催化功能之间的关系。与天然和重组野生型酶，底物...
The bioactivity of thyroid hormone is determined to a large extent by the monodeiodination of the prohormone T4 by the hepatic selenoenzyme type I iodothyronine deiodinase (ID1), i.e. by outer ring deiodination (ORD) to the active hormone T3, or by inner ring deiodination (IRD) to the inactive metabolite rT3. ID1 also catalyzes the IRD of T3 and the ORD of rT3, both to T2, as well as the deiodination of different iodothyronine sulfates, e.g. IRD of T3S and ORD of T2S. Previous studies have indicated important differences in catalytic specificity between dog ID1 (dID1) and human ID1 (hID1), in particular with respect to the ORD of rT3. This study was done to investigate the relationship between structure and catalytic function of this enzyme by comparing the deiodination of T4, T3, rT3, T3S, and T2S by native dID1 and hID1 in liver microsomes as well as by recombinant wild-type, chimeric and mutated d/hID1 enzymes expressed in HEK293 cells. With both native and recombinant wild-type enzymes, the substrate ...
登录
查看更多内容
基于人、狗和大鼠酶的比较功能结构分析，鉴定人 1 型脱碘酶对 3,5,3-三碘甲状腺原氨酸脱碘的关键氨基酸。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Toyoda,N;Harney,JW;Berry,MJ;Larsen,PR
通讯作者：
Larsen,PR
DOI：
10.1210/jcem.75.4.1400883
发表时间：
1992-10
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
S. Mandel;M. Berry;J. Kieffer;J. Harney;R. Warne;P. Larsen
通讯作者：
S. Mandel;M. Berry;J. Kieffer;J. Harney;R. Warne;P. Larsen
DOI：
10.1172/jci118299
发表时间：
1995-11
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
D. Salvatore;S. Low;M. Berry;A. Maia;John W. Hamey;W. Croteau;Donald;L. Germain;P. Larsen
通讯作者：
D. Salvatore;S. Low;M. Berry;A. Maia;John W. Hamey;W. Croteau;Donald;L. Germain;P. Larsen
遗传性 1 型脱碘酶缺乏症小鼠 dio1 基因的结构和功能差异。
DOI：
10.1210/mend.9.8.7476994
发表时间：
1995
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Maia,AL;Berry,MJ;Sabbag,R;Harney,JW;Larsen,PR
通讯作者：
Larsen,PR