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1j1b

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Revision as of 15:29, 12 November 2007 by OCA (Talk | contribs)
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1j1b, resolution 1.8Å

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Binary complex structure of human tau protein kinase I with AMPPNP

Overview

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.

About this Structure

1J1B is a Single protein structure of sequence from Homo sapiens with ANP as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

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

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