2pmf: Difference between revisions

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[[Image:2pmf.gif|left|200px]]
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{{STRUCTURE_2pmf|  PDB=2pmf  |  SCENE=  }}  
{{STRUCTURE_2pmf|  PDB=2pmf  |  SCENE=  }}  


'''The crystal structure of a human glycyl-tRNA synthetase mutant'''
===The crystal structure of a human glycyl-tRNA synthetase mutant===




==Overview==
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Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located approximately 30 A away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.
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{{ABSTRACT_PUBMED_17545306}}


==Disease==
==Disease==
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[[Category: Xie, W.]]
[[Category: Xie, W.]]
[[Category: Classiia aminoacyl-trna synthetase]]
[[Category: Classiia aminoacyl-trna synthetase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 13:24:49 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:11:53 2008''

Revision as of 14:11, 27 July 2008

File:2pmf.png

Template:STRUCTURE 2pmf

The crystal structure of a human glycyl-tRNA synthetase mutantThe crystal structure of a human glycyl-tRNA synthetase mutant

Template:ABSTRACT PUBMED 17545306

DiseaseDisease

Known disease associated with this structure: Charcot-Marie-Tooth disease, type 2D OMIM:[600287], Neuropathy, distal hereditary motor, type V OMIM:[600287]

About this StructureAbout this Structure

2PMF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase., Xie W, Nangle LA, Zhang W, Schimmel P, Yang XL, Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):9976-81. Epub 2007 Jun 1. PMID:17545306

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