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2q5h

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(New page: 200px<br /> <applet load="2q5h" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q5h, resolution 3.0&Aring;" /> '''Crystal structure of...)
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[[Image:2q5h.gif|left|200px]]<br />
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[[Image:2q5h.jpg|left|200px]]<br /><applet load="2q5h" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="2q5h" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="2q5h, resolution 3.0&Aring;" />
caption="2q5h, resolution 3.0&Aring;" />
'''Crystal structure of apo-wildtype Glycyl-tRNA synthetase'''<br />
'''Crystal structure of apo-wildtype Glycyl-tRNA synthetase'''<br />
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==Overview==
==Overview==
Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase, (GlyRS), including S581L, lead to motor nerve degeneration. We have, determined crystal structures of wildtype and S581L-mutant human GlyRS., The S581L mutation is approximately 50A from the active site, and yet, gives reduced aminoacylation activity. The overall structures of wildtype, and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in, turn could indirectly affect glycine binding via the tRNA or alternatively, inhibit conformational changes. Reduced enzyme activity may underlie, neuronal degeneration, although a dominant-negative effect is more likely, in this autosomal dominant disorder.
Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase, (GlyRS), including S581L, lead to motor nerve degeneration. We have, determined crystal structures of wildtype and S581L-mutant human GlyRS., The S581L mutation is approximately 50A from the active site, and yet, gives reduced aminoacylation activity. The overall structures of wildtype, and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in, turn could indirectly affect glycine binding via the tRNA or alternatively, inhibit conformational changes. Reduced enzyme activity may underlie, neuronal degeneration, although a dominant-negative effect is more likely, in this autosomal dominant disorder.
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==Disease==
 
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Known diseases associated with this structure: Charcot-Marie-Tooth disease, type 2D OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600287 600287]], Neuropathy, distal hereditary motor, type V OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600287 600287]]
 
==About this Structure==
==About this Structure==
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2Q5H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Glycine--tRNA_ligase Glycine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.14 6.1.1.14] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2Q5H OCA].
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2Q5H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Glycine--tRNA_ligase Glycine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.14 6.1.1.14] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q5H OCA].
==Reference==
==Reference==
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[[Category: structural genomics]]
[[Category: structural genomics]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:29:53 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:23:26 2008''

Revision as of 12:23, 23 January 2008


2q5h, resolution 3.0Å

Drag the structure with the mouse to rotate

Crystal structure of apo-wildtype Glycyl-tRNA synthetase

Overview

Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase, (GlyRS), including S581L, lead to motor nerve degeneration. We have, determined crystal structures of wildtype and S581L-mutant human GlyRS., The S581L mutation is approximately 50A from the active site, and yet, gives reduced aminoacylation activity. The overall structures of wildtype, and S581L-GlyRS, including the active site, are very similar. However, residues 567-575 of the anticodon-binding domain shift position and in, turn could indirectly affect glycine binding via the tRNA or alternatively, inhibit conformational changes. Reduced enzyme activity may underlie, neuronal degeneration, although a dominant-negative effect is more likely, in this autosomal dominant disorder.

About this Structure

2Q5H is a Single protein structure of sequence from Homo sapiens. Active as Glycine--tRNA ligase, with EC number 6.1.1.14 Full crystallographic information is available from OCA.

Reference

Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy., Cader MZ, Ren J, James PA, Bird LE, Talbot K, Stammers DK, FEBS Lett. 2007 Jun 26;581(16):2959-2964. Epub 2007 May 29. PMID:17544401

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