2uzs

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spinqualitylabelsall models 2uzs, resolution 2.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)

Overview

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is, a central member of possibly the most frequently activated proliferation, and survival pathway in cancer, mutation of AKT1 has not been widely, reported. Here we report the identification of a somatic mutation in human, breast, colorectal and ovarian cancers that results in a glutamic acid to, lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of, AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms, new hydrogen bonds with a phosphoinositide ligand. This mutation activates, AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia, in mice. This mechanism indicates a direct role of AKT1 in ... [(full description)]

About this Structure

2UZS is a [Single protein] structure of sequence from [Homo sapiens] with ACE and 4IP as [ligands]. Active as [Non-specific serine/threonine protein kinase], with EC number [2.7.11.1]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

Reference

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer., Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE, Nature. 2007 Jul 26;448(7152):439-44. Epub 2007 Jul 4. PMID:17611497

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