2det
From Proteopedia
(New page: 200px<br /><applet load="2det" size="450" color="white" frame="true" align="right" spinBox="true" caption="2det, resolution 3.40Å" /> '''Cocrystal structure ...) |
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| - | [[Image:2det.gif|left|200px]]<br /><applet load="2det" size=" | + | [[Image:2det.gif|left|200px]]<br /><applet load="2det" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2det, resolution 3.40Å" /> | caption="2det, resolution 3.40Å" /> | ||
'''Cocrystal structure of an RNA sulfuration enzyme MnmA and tRNA-Glu in the pre-reaction state'''<br /> | '''Cocrystal structure of an RNA sulfuration enzyme MnmA and tRNA-Glu in the pre-reaction state'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Uridine at the first anticodon position (U34) of glutamate, lysine and | + | Uridine at the first anticodon position (U34) of glutamate, lysine and glutamine transfer RNAs is universally modified by thiouridylase into 2-thiouridine (s2U34), which is crucial for precise translation by restricting codon-anticodon wobble during protein synthesis on the ribosome. However, it remains unclear how the enzyme incorporates reactive sulphur into the correct position of the uridine base. Here we present the crystal structures of the MnmA thiouridylase-tRNA complex in three discrete forms, which provide snapshots of the sequential chemical reactions during RNA sulphuration. On enzyme activation, an alpha-helix overhanging the active site is restructured into an idiosyncratic beta-hairpin-containing loop, which packs the flipped-out U34 deeply into the catalytic pocket and triggers the activation of the catalytic cysteine residues. The adenylated RNA intermediate is trapped. Thus, the active closed-conformation of the complex ensures accurate sulphur incorporation into the activated uridine carbon by forming a catalytic chamber to prevent solvent from accessing the catalytic site. The structures of the complex with glutamate tRNA further reveal how MnmA specifically recognizes its three different tRNA substrates. These findings provide the structural basis for a general mechanism whereby an enzyme incorporates a reactive atom at a precise position in a biological molecule. |
==About this Structure== | ==About this Structure== | ||
| - | 2DET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/tRNA_(5-methylaminomethyl-2-thiouridylate)-methyltransferase tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.61 2.1.1.61] Full crystallographic information is available from [http:// | + | 2DET is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/tRNA_(5-methylaminomethyl-2-thiouridylate)-methyltransferase tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.61 2.1.1.61] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DET OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-rna complex]] | [[Category: protein-rna complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:58:05 2008'' |
Revision as of 14:58, 21 February 2008
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Cocrystal structure of an RNA sulfuration enzyme MnmA and tRNA-Glu in the pre-reaction state
Overview
Uridine at the first anticodon position (U34) of glutamate, lysine and glutamine transfer RNAs is universally modified by thiouridylase into 2-thiouridine (s2U34), which is crucial for precise translation by restricting codon-anticodon wobble during protein synthesis on the ribosome. However, it remains unclear how the enzyme incorporates reactive sulphur into the correct position of the uridine base. Here we present the crystal structures of the MnmA thiouridylase-tRNA complex in three discrete forms, which provide snapshots of the sequential chemical reactions during RNA sulphuration. On enzyme activation, an alpha-helix overhanging the active site is restructured into an idiosyncratic beta-hairpin-containing loop, which packs the flipped-out U34 deeply into the catalytic pocket and triggers the activation of the catalytic cysteine residues. The adenylated RNA intermediate is trapped. Thus, the active closed-conformation of the complex ensures accurate sulphur incorporation into the activated uridine carbon by forming a catalytic chamber to prevent solvent from accessing the catalytic site. The structures of the complex with glutamate tRNA further reveal how MnmA specifically recognizes its three different tRNA substrates. These findings provide the structural basis for a general mechanism whereby an enzyme incorporates a reactive atom at a precise position in a biological molecule.
About this Structure
2DET is a Single protein structure of sequence from Escherichia coli with as ligand. Active as tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase, with EC number 2.1.1.61 Full crystallographic information is available from OCA.
Reference
Snapshots of tRNA sulphuration via an adenylated intermediate., Numata T, Ikeuchi Y, Fukai S, Suzuki T, Nureki O, Nature. 2006 Jul 27;442(7101):419-24. PMID:16871210
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