2pme: Difference between revisions
New page: left|200px<br /> <applet load="2pme" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pme, resolution 2.900Å" /> '''The Apo crystal St... |
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[[Image:2pme.gif|left|200px]]<br /> | [[Image:2pme.gif|left|200px]]<br /><applet load="2pme" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2pme, resolution 2.900Å" /> | caption="2pme, resolution 2.900Å" /> | ||
'''The Apo crystal Structure of the glycyl-tRNA synthetase'''<br /> | '''The Apo crystal Structure of the glycyl-tRNA synthetase'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2PME 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:// | 2PME 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=2PME OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: classiia aminoacyl trna synthetase]] | [[Category: classiia aminoacyl trna synthetase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:47:57 2008'' | ||
Revision as of 15:47, 23 January 2008
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The Apo crystal Structure of the glycyl-tRNA synthetase
OverviewOverview
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.
About this StructureAbout this Structure
2PME 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.
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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