1n3l

From Proteopedia

---

Revision as of 16:10, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1n3l, resolution 1.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of a human aminoacyl-tRNA synthetase cytokine

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The 20 aminoacyl-tRNA synthetases catalyze the first step of protein, synthesis and establish the rules of the genetic code through, aminoacylation reactions. Biological fragments of two human enzymes, tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase, connect, protein synthesis to cell-signaling pathways including angiogenesis., Alternative splicing or proteolysis produces these fragments. The, proangiogenic N-terminal fragment mini-TyrRS has IL-8-like cytokine, activity that, like other CXC cytokines, depends on a Glu-Leu-Arg motif., Point mutations in this motif abolish cytokine activity. The full-length, native TyrRS lacks cytokine activity. No structure has been available for, any mammalian tRNA synthetase that, in turn, might give insight into why, mini-TyrRS and not TyrRS has cytokine activities. Here, the structure of, human mini-TyrRS, which contains both the catalytic and the anticodon, recognition domain, is reported to a resolution of 1.18 A. The critical, Glu-Leu-Arg motif is located on an internal alpha-helix of the catalytic, domain, where the guanidino side chain of R is part of a hydrogen-bonding, network tethering the anticodon-recognition domain back to the catalytic, site. Whereas the catalytic domains of the human and bacterial enzymes, superimpose, the spatial disposition of the anticodon recognition domain, relative to the catalytic domain is unique in mini-TyrRS relative to the, bacterial orthologs. This unique orientation of the anticodon-recognition, domain can explain why the fragment mini-TyrRS, and not full-length native, TyrRS, is active in cytokine-signaling pathways.

Disease

Known disease associated with this structure: Charcot-Marie-Tooth disease, dominant intermediate C OMIM:[603623]

About this Structure

1N3L is a Single protein structure of sequence from Homo sapiens with SO4 and GOL as ligands. Active as Tyrosine--tRNA ligase, with EC number 6.1.1.1 Full crystallographic information is available from OCA.

Reference

Crystal structure of a human aminoacyl-tRNA synthetase cytokine., Yang XL, Skene RJ, McRee DE, Schimmel P, Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15369-74. Epub 2002 Nov 11. PMID:12427973

Page seeded by OCA on Mon Nov 12 18:17:25 2007