2q5h: Difference between revisions
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==Overview== | ==Overview== | ||
Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase | 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. | ||
==Disease== | |||
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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==Reference== | ==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- | 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):2959-64. Epub 2007 May 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17544401 17544401] | ||
[[Category: Glycine--tRNA ligase]] | [[Category: Glycine--tRNA ligase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bird, L | [[Category: Bird, L E.]] | ||
[[Category: Cader, M | [[Category: Cader, M Z.]] | ||
[[Category: James, P | [[Category: James, P A.]] | ||
[[Category: OPPF, Oxford | [[Category: OPPF, Oxford Protein Production Facility.]] | ||
[[Category: Ren, J.]] | [[Category: Ren, J.]] | ||
[[Category: Stammers, D | [[Category: Stammers, D K.]] | ||
[[Category: Talbot, K.]] | [[Category: Talbot, K.]] | ||
[[Category: aminoacyl-trna synthetase]] | [[Category: aminoacyl-trna synthetase]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:11 2008'' | ||
Revision as of 19:36, 21 February 2008
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Crystal structure of apo-wildtype Glycyl-tRNA synthetase
OverviewOverview
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.
DiseaseDisease
Known diseases 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
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.
ReferenceReference
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):2959-64. Epub 2007 May 29. PMID:17544401
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