1ksw

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spinqualitylabelsall models 1ksw, resolution 2.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of Human c-Src Tyrosine Kinase (Thr338Gly Mutant) in Complex with N6-benzyl ADP

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The direct substrates of one protein kinase in a cell can be identified by, mutation of the ATP binding pocket to allow an unnatural ATP analog to be, accepted exclusively by the engineered kinase. Here, we present structural, and functional assessment of peptide specificity of mutant protein kinases, with unnatural ATP analogs. The crystal structure (2.8 A resolution) of, c-Src (T338G) with N(6)-(benzyl) ADP bound shows that the creation of a, unique nucleotide binding pocket does not alter the phospho-acceptor, binding site of the kinase. A panel of optimal peptide substrates of, defined sequence, as well as a degenerate peptide library, was utilized to, assess the phospho-acceptor specificity of the engineered "traceable", kinases. The specificity profiles for the mutant kinases were found to be, identical to those of their wild-type counterparts.

Disease

Known disease associated with this structure: Colon cancer, advanced OMIM:[190090]

About this Structure

1KSW is a Single protein structure of sequence from Homo sapiens with NBS as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

Mutant tyrosine kinases with unnatural nucleotide specificity retain the structure and phospho-acceptor specificity of the wild-type enzyme., Witucki LA, Huang X, Shah K, Liu Y, Kyin S, Eck MJ, Shokat KM, Chem Biol. 2002 Jan;9(1):25-33. PMID:11841936

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