1jzq
From Proteopedia
(New page: 200px<br /><applet load="1jzq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jzq, resolution 3.0Å" /> '''Isoleucyl-tRNA synthe...) |
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| - | [[Image:1jzq.gif|left|200px]]<br /><applet load="1jzq" size=" | + | [[Image:1jzq.gif|left|200px]]<br /><applet load="1jzq" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jzq, resolution 3.0Å" /> | caption="1jzq, resolution 3.0Å" /> | ||
'''Isoleucyl-tRNA synthetase Complexed with Isoleucyl-adenylate analogue'''<br /> | '''Isoleucyl-tRNA synthetase Complexed with Isoleucyl-adenylate analogue'''<br /> | ||
==Overview== | ==Overview== | ||
| - | An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the | + | An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistant Staphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium, Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-A resolutions, respectively. A structural comparison of the IleRS.Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin. |
==About this Structure== | ==About this Structure== | ||
| - | 1JZQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with ZN and ILA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isoleucine--tRNA_ligase Isoleucine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.5 6.1.1.5] Full crystallographic information is available from [http:// | + | 1JZQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=ILA:'>ILA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isoleucine--tRNA_ligase Isoleucine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.5 6.1.1.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JZQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Nakama, T.]] | [[Category: Nakama, T.]] | ||
[[Category: Nureki, O.]] | [[Category: Nureki, O.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Yokoyama, S.]] | [[Category: Yokoyama, S.]] | ||
[[Category: ILA]] | [[Category: ILA]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:28:30 2008'' |
Revision as of 11:28, 21 February 2008
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Isoleucyl-tRNA synthetase Complexed with Isoleucyl-adenylate analogue
Overview
An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistant Staphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium, Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-A resolutions, respectively. A structural comparison of the IleRS.Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin.
About this Structure
1JZQ is a Single protein structure of sequence from Thermus thermophilus with and as ligands. Active as Isoleucine--tRNA ligase, with EC number 6.1.1.5 Full crystallographic information is available from OCA.
Reference
Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase., Nakama T, Nureki O, Yokoyama S, J Biol Chem. 2001 Dec 14;276(50):47387-93. Epub 2001 Oct 2. PMID:11584022
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