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Human tau-protein kinase I (TPK I; also known as glycogen synthase kinase 3 beta; GSK3 beta) is a serine/threonine protein kinase that participates in Alzheimer's disease. Here, binary complex structures of full-length TPK I/GSK3 beta with the ATP analogues ADP and AMPPNP solved by the X-ray diffraction method at 2.1 and 1.8 A resolution, respectively, are reported. TPK I/GSK3 beta 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/GSK3 beta. No residues are phosphorylated, while the orientation of the activation loop in TPK I/GSK3 beta is similar to that in phosphorylated CDK2 and ERK2, suggesting that TPK I/GSK3 beta falls into a conformation that enables it to be constitutively active.

Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta., Aoki M, Yokota T, Sugiura I, Sasaki C, Hasegawa T, Okumura C, Ishiguro K, Kohno T, Sugio S, Matsuzaki T, Acta Crystallogr D Biol Crystallogr. 2004 Mar;60(Pt 3):439-46. Epub 2004, Feb 25. PMID:14993667

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Aoki, M. | Hasegawa, T. | Kohno, T. | Matsuzaki, T. | Okumura, C. | Sasaki, C. | Sugio, S. | Sugiura, I. | Yokota, T. | Adp | Complex | Kinase | Tau