1yfs
From Proteopedia
(New page: 200px<br /><applet load="1yfs" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yfs, resolution 2.08Å" /> '''The crystal structur...) |
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| - | [[Image:1yfs.gif|left|200px]]<br /><applet load="1yfs" size=" | + | [[Image:1yfs.gif|left|200px]]<br /><applet load="1yfs" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yfs, resolution 2.08Å" /> | caption="1yfs, resolution 2.08Å" /> | ||
'''The crystal structure of alanyl-tRNA synthetase in complex with L-alanine'''<br /> | '''The crystal structure of alanyl-tRNA synthetase in complex with L-alanine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The genetic code is fixed in aminoacylation reactions catalyzed by | + | The genetic code is fixed in aminoacylation reactions catalyzed by aminoacyl-tRNA synthetases. Amino acid discrimination occurs at two sites: one for amino acid activation and aminoacylation and one for editing misactivated amino acids. Although the active site sieves out bulkier amino acids, misactivation occurs with substrates whose side chains are smaller than the cognate one. Paradoxically, although alanyl-tRNA synthetase activates glycine as well as alanine, the sterically larger (than alanine) serine is also misactivated. Here, we report crystal structures of an active fragment of Aquifex aeolicus alanyl-tRNA synthetase complexed, separately, with Mg2+-ATP, alanine, glycine, and serine. Ala and Gly are bound in similar orientations in a side-chain-accommodating pocket, where alpha-amino and carboxyl groups are stabilized by salt bridges, and the carboxyl by an H-bond from the side chain NH2 of Asn-194. In contrast, whereas the same two salt bridges stabilize bound Ser, H-bonding of the highly conserved (among class II tRNA synthetases) Asn-194 side chain NH2 to the Ser OH, instead of to the carboxyl, forces pocket expansion. Significantly, in the Mg2+-ATP complex, Asn-194 coordinates a Mg2+-alpha-phosphate bridge. Thus, the sieve for Ser exclusion is broken because of selective pressure to retain Asn-194 for Mg2+-ATP and Ala binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1YFS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with ALA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine--tRNA_ligase Alanine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.7 6.1.1.7] Full crystallographic information is available from [http:// | + | 1YFS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with <scene name='pdbligand=ALA:'>ALA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine--tRNA_ligase Alanine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.7 6.1.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YFS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Schimmel, P | + | [[Category: Schimmel, P R.]] |
| - | [[Category: Swairjo, M | + | [[Category: Swairjo, M A.]] |
[[Category: ALA]] | [[Category: ALA]] | ||
[[Category: alpha-beta fold]] | [[Category: alpha-beta fold]] | ||
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[[Category: helix-loop-helix motif]] | [[Category: helix-loop-helix motif]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:04:53 2008'' |
Revision as of 14:04, 21 February 2008
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The crystal structure of alanyl-tRNA synthetase in complex with L-alanine
Overview
The genetic code is fixed in aminoacylation reactions catalyzed by aminoacyl-tRNA synthetases. Amino acid discrimination occurs at two sites: one for amino acid activation and aminoacylation and one for editing misactivated amino acids. Although the active site sieves out bulkier amino acids, misactivation occurs with substrates whose side chains are smaller than the cognate one. Paradoxically, although alanyl-tRNA synthetase activates glycine as well as alanine, the sterically larger (than alanine) serine is also misactivated. Here, we report crystal structures of an active fragment of Aquifex aeolicus alanyl-tRNA synthetase complexed, separately, with Mg2+-ATP, alanine, glycine, and serine. Ala and Gly are bound in similar orientations in a side-chain-accommodating pocket, where alpha-amino and carboxyl groups are stabilized by salt bridges, and the carboxyl by an H-bond from the side chain NH2 of Asn-194. In contrast, whereas the same two salt bridges stabilize bound Ser, H-bonding of the highly conserved (among class II tRNA synthetases) Asn-194 side chain NH2 to the Ser OH, instead of to the carboxyl, forces pocket expansion. Significantly, in the Mg2+-ATP complex, Asn-194 coordinates a Mg2+-alpha-phosphate bridge. Thus, the sieve for Ser exclusion is broken because of selective pressure to retain Asn-194 for Mg2+-ATP and Ala binding.
About this Structure
1YFS is a Single protein structure of sequence from Aquifex aeolicus with as ligand. Active as Alanine--tRNA ligase, with EC number 6.1.1.7 Full crystallographic information is available from OCA.
Reference
Breaking sieve for steric exclusion of a noncognate amino acid from active site of a tRNA synthetase., Swairjo MA, Schimmel PR, Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):988-93. Epub 2005 Jan 18. PMID:15657145
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