2ag6: Difference between revisions

Revision as of 17:27, 21 February 2008

Crystal structure of p-bromo-l-phenylalanine-tRNA sythetase in complex with p-bromo-l-phenylalanine

OverviewOverview

Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one to genetically encode a large array of unnatural amino acids in both prokaryotic and eukaryotic organisms. We have determined the crystal structures of two substrate-bound Methanococcus jannaschii tyrosyl aminoacyl-tRNA synthetases that charge the unnatural amino acids p-bromophenylalanine and 3-(2-naphthyl)alanine (NpAla). A comparison of these structures with the substrate-bound WT synthetase, as well as a mutant synthetase that charges p-acetylphenylalanine, shows that altered specificity is due to both side-chain and backbone rearrangements within the active site that modify hydrogen bonds and packing interactions with substrate, as well as disrupt the alpha8-helix, which spans the WT active site. The high degree of structural plasticity that is observed in these aminoacyl-tRNA synthetases is rarely found in other mutant enzymes with altered specificities and provides an explanation for the surprising adaptability of the genetic code to novel amino acids.

About this StructureAbout this Structure

2AG6 is a Single protein structure of sequence from Methanocaldococcus jannaschii with as ligand. Active as Tyrosine--tRNA ligase, with EC number 6.1.1.1 Full crystallographic information is available from OCA.

ReferenceReference

Structural plasticity of an aminoacyl-tRNA synthetase active site., Turner JM, Graziano J, Spraggon G, Schultz PG, Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6483-8. Epub 2006 Apr 17. PMID:16618920

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OCA

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-[[Image:2ag6.gif|left|200px]]<br /><applet load="2ag6" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2ag6.gif|left|200px]]<br /><applet load="2ag6" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2ag6, resolution 1.90&Aring;" />
 '''Crystal structure of p-bromo-l-phenylalanine-tRNA sythetase in complex with p-bromo-l-phenylalanine'''<br />
 ==Overview==
-Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that, allow one to genetically encode a large array of unnatural amino acids in, both prokaryotic and eukaryotic organisms. We have determined the crystal, structures of two substrate-bound Methanococcus jannaschii tyrosyl, aminoacyl-tRNA synthetases that charge the unnatural amino acids, p-bromophenylalanine and 3-(2-naphthyl)alanine (NpAla). A comparison of, these structures with the substrate-bound WT synthetase, as well as a, mutant synthetase that charges p-acetylphenylalanine, shows that altered, specificity is due to both side-chain and backbone rearrangements within, the active site that modify hydrogen bonds and packing interactions with, substrate, as well as disrupt the alpha8-helix, which spans the WT active, site. The high degree of structural plasticity that is observed in these, aminoacyl-tRNA synthetases is rarely found in other mutant enzymes with, altered specificities and provides an explanation for the surprising, adaptability of the genetic code to novel amino acids.
+Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one to genetically encode a large array of unnatural amino acids in both prokaryotic and eukaryotic organisms. We have determined the crystal structures of two substrate-bound Methanococcus jannaschii tyrosyl aminoacyl-tRNA synthetases that charge the unnatural amino acids p-bromophenylalanine and 3-(2-naphthyl)alanine (NpAla). A comparison of these structures with the substrate-bound WT synthetase, as well as a mutant synthetase that charges p-acetylphenylalanine, shows that altered specificity is due to both side-chain and backbone rearrangements within the active site that modify hydrogen bonds and packing interactions with substrate, as well as disrupt the alpha8-helix, which spans the WT active site. The high degree of structural plasticity that is observed in these aminoacyl-tRNA synthetases is rarely found in other mutant enzymes with altered specificities and provides an explanation for the surprising adaptability of the genetic code to novel amino acids.
 ==About this Structure==
-AG6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with 4BF as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tyrosine--tRNA_ligase Tyrosine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.1 6.1.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AG6 OCA].
+AG6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanocaldococcus_jannaschii Methanocaldococcus jannaschii] with <scene name='pdbligand=4BF:'>4BF</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tyrosine--tRNA_ligase Tyrosine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.1 6.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AG6 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Tyrosine--tRNA ligase]]
 [[Category: Graziano, J.]]
-[[Category: Schultz, P.G.]]
+[[Category: Schultz, P G.]]
 [[Category: Spraggon, G.]]
-[[Category: Turner, J.M.]]
+[[Category: Turner, J M.]]
 [[Category: 4BF]]
 [[Category: bromo-phenylalanine]]
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 [[Category: unnatural amino acid]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:06:09 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:27:05 2008''