1nj2: Difference between revisions

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Crystal structure of Prolyl-tRNA Synthetase from Methanothermobacter thermautotrophicus

OverviewOverview

Cysteinyl-tRNA synthetase is an essential enzyme required for protein synthesis. Genes encoding this protein have not been identified in Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, or Methanopyrus kandleri. It has previously been proposed that the prolyl-tRNA synthetase (ProRS) enzymes in these organisms recognize either proline or cysteine and can aminoacylate their cognate tRNAs through a dual-specificity mechanism. We report five crystal structures at resolutions between 2.6 and 3.2 A: apo M. jannaschii ProRS, and M. thermautotrophicus ProRS in apo form and in complex with cysteinyl-sulfamoyl-, prolyl-sulfamoyl-, and alanyl-sulfamoyl-adenylates. These aminoacyl-adenylate analogues bind to a single active-site pocket and induce an identical set of conformational changes in loops around the active site when compared with the ligand-free conformation of ProRS. The cysteinyl- and prolyl-adenylate analogues have similar, nanomolar affinities for M. thermautotrophicus ProRS. Homology modeling of tRNA onto these adenylate complexes places the 3'-OH of A76 in an appropriate position for the transfer of any of the three amino acids to tRNA. Thus, these structures explain recent biochemical experiments showing that M. jannaschii ProRS misacylates tRNA(Pro) with cysteine, and argue against the proposal that these archaeal ProRS enzymes possess the dual capacity to aminoacylate both tRNA(Pro) and tRNA(Cys) with their cognate amino acids.

About this StructureAbout this Structure

1NJ2 is a Single protein structure of sequence from Methanothermobacter thermautotrophicus with and as ligands. Active as Proline--tRNA ligase, with EC number 6.1.1.15 Full crystallographic information is available from OCA.

ReferenceReference

The structural basis of cysteine aminoacylation of tRNAPro by prolyl-tRNA synthetases., Kamtekar S, Kennedy WD, Wang J, Stathopoulos C, Soll D, Steitz TA, Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1673-8. Epub 2003 Feb 10. PMID:12578991

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 '''Crystal structure of Prolyl-tRNA Synthetase from Methanothermobacter thermautotrophicus'''<br />
 ==Overview==
-Cysteinyl-tRNA synthetase is an essential enzyme required for protein, synthesis. Genes encoding this protein have not been identified in, Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, or, Methanopyrus kandleri. It has previously been proposed that the, prolyl-tRNA synthetase (ProRS) enzymes in these organisms recognize either, proline or cysteine and can aminoacylate their cognate tRNAs through a, dual-specificity mechanism. We report five crystal structures at, resolutions between 2.6 and 3.2 A: apo M. jannaschii ProRS, and M., thermautotrophicus ProRS in apo form and in complex with, cysteinyl-sulfamoyl-, prolyl-sulfamoyl-, and alanyl-sulfamoyl-adenylates., These aminoacyl-adenylate analogues bind to a single active-site pocket, and induce an identical set of conformational changes in loops around the, active site when compared with the ligand-free conformation of ProRS. The, cysteinyl- and prolyl-adenylate analogues have similar, nanomolar, affinities for M. thermautotrophicus ProRS. Homology modeling of tRNA onto, these adenylate complexes places the 3'-OH of A76 in an appropriate, position for the transfer of any of the three amino acids to tRNA. Thus, these structures explain recent biochemical experiments showing that M., jannaschii ProRS misacylates tRNA(Pro) with cysteine, and argue against, the proposal that these archaeal ProRS enzymes possess the dual capacity, to aminoacylate both tRNA(Pro) and tRNA(Cys) with their cognate amino, acids.
+Cysteinyl-tRNA synthetase is an essential enzyme required for protein synthesis. Genes encoding this protein have not been identified in Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, or Methanopyrus kandleri. It has previously been proposed that the prolyl-tRNA synthetase (ProRS) enzymes in these organisms recognize either proline or cysteine and can aminoacylate their cognate tRNAs through a dual-specificity mechanism. We report five crystal structures at resolutions between 2.6 and 3.2 A: apo M. jannaschii ProRS, and M. thermautotrophicus ProRS in apo form and in complex with cysteinyl-sulfamoyl-, prolyl-sulfamoyl-, and alanyl-sulfamoyl-adenylates. These aminoacyl-adenylate analogues bind to a single active-site pocket and induce an identical set of conformational changes in loops around the active site when compared with the ligand-free conformation of ProRS. The cysteinyl- and prolyl-adenylate analogues have similar, nanomolar affinities for M. thermautotrophicus ProRS. Homology modeling of tRNA onto these adenylate complexes places the 3'-OH of A76 in an appropriate position for the transfer of any of the three amino acids to tRNA. Thus, these structures explain recent biochemical experiments showing that M. jannaschii ProRS misacylates tRNA(Pro) with cysteine, and argue against the proposal that these archaeal ProRS enzymes possess the dual capacity to aminoacylate both tRNA(Pro) and tRNA(Cys) with their cognate amino acids.
 ==About this Structure==
-NJ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with ZN and MG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NJ2 OCA].
+NJ2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Proline--tRNA_ligase Proline--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.15 6.1.1.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NJ2 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Kamtekar, S.]]
-[[Category: Kennedy, W.D.]]
+[[Category: Kennedy, W D.]]
 [[Category: Soll, D.]]
 [[Category: Stathopoulos, C.]]
-[[Category: Steitz, T.A.]]
+[[Category: Steitz, T A.]]
 [[Category: Wang, J.]]
 [[Category: MG]]
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 [[Category: class-ii trna synthetase]]
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