2pmf: Difference between revisions
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New page: left|200px<br /> <applet load="2pmf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pmf, resolution 2.850Å" /> '''The crystal struct... |
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[[Image:2pmf.gif|left|200px]]<br /> | [[Image:2pmf.gif|left|200px]]<br /><applet load="2pmf" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2pmf" size=" | |||
caption="2pmf, resolution 2.850Å" /> | caption="2pmf, resolution 2.850Å" /> | ||
'''The crystal structure of a human glycyl-tRNA synthetase mutant'''<br /> | '''The crystal structure of a human glycyl-tRNA synthetase mutant'''<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== | ||
2PMF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 2PMF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2PMF 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 14:48:01 2008'' | ||
