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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta
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Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta

机译：结构洞察核苷酸识别tau蛋白激酶I /糖原合成酶激酶3β

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摘要

Human tau-protein kinase I (TPK I; also known as glycogen synthase kinase 3beta; GSK3beta) is a serine/threonine protein kinase that participates in Alzheimer's disease. Here, binary complex structures of full-length TPK I/GSK3beta with the ATP analogues ADP and AMPPNP solved by the X-ray diffraction method at 2.1 and 1.8 Angstrom resolution, respectively, are reported. TPK I/GSK3beta is composed of three domains: an N-terminal domain consisting of a closed beta-barrel structure, a C-terminal domain containing a 'kinase fold' structure and a small extra-domain subsequent to the C-terminal domain. The catalytic site is between the two major domains and has an ATP-analogue molecule in its ATP-binding site. The adenine ring is buried in the hydrophobic pocket and interacts specifically with the main-chain atoms of the hinge loop. The overall structure and substrate-binding residues are similar to those observed in other Ser/Thr protein kinases, while Arg141 (which is not conserved among other Ser/Thr protein kinases) is one of the key residues for specific ATP/ADP recognition by TPK I/GSK3beta. No residues are phosphorylated, while the orientation of the activation loop in TPK I/GSK3beta is similar to that in phosphorylated CDK2 and ERK2, suggesting that TPK I/GSK3beta falls into a conformation that enables it to be constitutively active.
机译：人类tau蛋白激酶I (TPK我;糖原合成酶激酶3β;丝氨酸/苏氨酸蛋白激酶,参与在阿尔茨海默氏症。结构完整的TPK我/ GSK3beta三磷酸腺苷类似物ADP和AMPPNP通过x射线来解决在2.1和1.8埃衍射法分辨率,分别报告。我/ GSK3beta由三个领域:一个n端结构域组成的一个封闭的beta-barrel结构,c端域包含一个激酶折叠的结构和一个小extra-domain后续c端域。之间的两个主要催化部位域和ATP-analogue分子的磷酸腺苷的网站。疏水口袋和交互的主链原子铰链循环。总体结构和substrate-binding残留物类似于那些在其他对丝氨酸/苏氨酸吗蛋白激酶,Arg141(这不是守恒等对丝氨酸/苏氨酸蛋白激酶)一个关键的为特定的ATP / ADP残留通过TPK I / GSK3beta认可。磷酸化,的方向激活循环TPK I / GSK3beta相似在磷酸化CDK2 ERK2,建议TPK I / GSK3beta落入一个构象使它持续活跃。

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