新的NADPH结合域由阿尔多减少酶的晶体结构揭示出来
J M Rondeau1, F Tête-Favier, A Podjarny
1Laboratoire de Cristallographie Biologique, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
Nature
|January 30, 1992
概括
在糖尿病并发症中关键的阿尔多斯减少酶被结构性分析. 它独特的α/β桶结构揭示了尼古丁胺胺二核酸共酶的新型结合部位.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 阿尔多减少酶启动了多路径,将D-葡萄糖转化为D-醇.
- 虽然对于度调节至关重要,但阿尔多减少酶活性会加剧高血糖症下的糖尿病并发症.
- 了解阿尔多减少酶结构对于开发向疗法至关重要.
研究的目的:
- 为了确定猪透镜的晶体结构,阿尔多减少酶.
- 为了阐明尼古丁胺胺氨基二核酸 (NADPH) 共酶的结合机制.
主要方法:
- 采用X射线晶体学,获得了猪透镜的阿尔多缩小酶结构.
- 该结构在2.5A分辨率下改进到0.232的R系数.
- 进行了抑制剂结合的晶体分析.
主要成果:
- 猪透镜阿尔多减少酶结构揭示了一个由八链平行α/β桶组成的单个域.
- 这种结构偏离了预期的正规二核酸结合域.
- 2'-单-腺-5'-二二酶可以竞争性地抑制NADPH结合,局部化到桶的C端端的裂.
结论:
- 阿尔多缩小酶具有独特的结构折叠,此前未曾预计用于结合尼古丁胺胺氨酸二核酸共酶的酶.
- 鉴定到的结合部位代表了一种新的辅酶相互作用模式.
- 这种结构洞察力可能会为设计新的阿尔多缩酶抑制剂提供信息,用于管理糖尿病并发症.
更多相关视频
12:07Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
Published on: October 9, 2021
13:35Structural Biology and Analytical Chemistry Approaches for Characterizing C-Glycoside Metabolic Enzymes in Human Gut Microbiota
Published on: May 23, 2025
相关概念视频
Photosystem I
Although structurally similar to photosystem II (PSII), photosystem I (PSI) is has a different electron supplier and electron acceptor.
Both these photosystems work in concert. An excited electron from PSII is relayed to PSI via an electron transport chain in the thylakoid membrane of the chloroplast, which is comprised of the carrier molecule plastoquinone, the dual-protein cytochrome complex, and plastocyanin. As electrons move between PSII and PSI, they lose energy and must be re-energized...
Both these photosystems work in concert. An excited electron from PSII is relayed to PSI via an electron transport chain in the thylakoid membrane of the chloroplast, which is comprised of the carrier molecule plastoquinone, the dual-protein cytochrome complex, and plastocyanin. As electrons move between PSII and PSI, they lose energy and must be re-energized...
The Antenna Complex
Plants and other photosynthetic organisms comprise pigments capable of absorption of direct sunlight. These pigments are present in the reaction center - the main site of photochemical reactions as well as in the antenna complex. Under average light conditions, the rate at which reaction center pigments absorb light is far below the electron transport chain's capacity. As a result, the reaction center alone cannot provide enough energy to drive photosynthesis. The photosynthetic efficiency can...
The Z-Scheme of Electron Transport in Photosynthesis
The light reactions of photosynthesis assume a linear flow of electrons from water to NADP+. During this process, light energy drives the splitting of water molecules to produce oxygen. However, oxidation of water molecules is a thermodynamically unfavorable reaction and requires a strong oxidizing agent. This is accomplished by the first product of light reactions: oxidized P680 (or P680+), the most powerful oxidizing agent known in biology. The oxidized P680 that acquires an electron from the...
ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
Role of Reduced Coenzymes NADH and FADH₂
The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...
