2v0g: Difference between revisions

Revision as of 17:57, 4 May 2008

LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A TRNA(LEU) TRANSCRIPT WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) FORMING AN ADDUCT TO THE RIBOSE OF ADENOSINE-76 IN THE ENZYME EDITING SITE.

OverviewOverview

Aminoacyl-transfer RNA (tRNA) synthetases, which catalyze the attachment of the correct amino acid to its corresponding tRNA during translation of the genetic code, are proven antimicrobial drug targets. We show that the broad-spectrum antifungal 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), in development for the treatment of onychomycosis, inhibits yeast cytoplasmic leucyl-tRNA synthetase by formation of a stable tRNA(Leu)-AN2690 adduct in the editing site of the enzyme. Adduct formation is mediated through the boron atom of AN2690 and the 2'- and 3'-oxygen atoms of tRNA's3'-terminal adenosine. The trapping of enzyme-bound tRNA(Leu) in the editing site prevents catalytic turnover, thus inhibiting synthesis of leucyl-tRNA(Leu) and consequentially blocking protein synthesis. This result establishes the editing site as a bona fide target for aminoacyl-tRNA synthetase inhibitors.

About this StructureAbout this Structure

2V0G is a Protein complex structure of sequences from Thermus thermophilus. Full crystallographic information is available from OCA.

ReferenceReference

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site., Rock FL, Mao W, Yaremchuk A, Tukalo M, Crepin T, Zhou H, Zhang YK, Hernandez V, Akama T, Baker SJ, Plattner JJ, Shapiro L, Martinis SA, Benkovic SJ, Cusack S, Alley MR, Science. 2007 Jun 22;316(5832):1759-61. PMID:17588934 Page seeded by OCA on Sun May 4 17:57:43 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2v0g.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2v0g |SIZE=350|CAPTION= <scene name='initialview01'>2v0g</scene>, resolution 3.50&Aring;
+The line below this paragraph, containing "STRUCTURE_2v0g", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:LEU+Binding+Site+For+Chain+D'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=A:ADENOSINE-5&#39;-MONOPHOSPHATE'>A</scene>, <scene name='pdbligand=ANZ:[(6-AMINO-9H-PURIN-9-YL)-[5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE]-4&#39;YL]METHYL+DIHYDROGEN+PHOSPHATE'>ANZ</scene>, <scene name='pdbligand=C:CYTIDINE-5&#39;-MONOPHOSPHATE'>C</scene>, <scene name='pdbligand=G:GUANOSINE-5&#39;-MONOPHOSPHATE'>G</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=U:URIDINE-5&#39;-MONOPHOSPHATE'>U</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2v0g|  PDB=2v0g  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v0g OCA], [http://www.ebi.ac.uk/pdbsum/2v0g PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2v0g RCSB]</span>
-}}
 '''LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A TRNA(LEU) TRANSCRIPT WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) FORMING AN ADDUCT TO THE RIBOSE OF ADENOSINE-76 IN THE ENZYME EDITING SITE.'''
@@ Line 41: / Line 38: @@
 [[Category: Zhang, Y.]]
 [[Category: Zhou, H.]]
-[[Category: aminoacyl-trna synthetase]]
+[[Category: Aminoacyl-trna synthetase]]
-[[Category: atp + l-leucine + trna (leu) gives amp + ppi l-leucyl-trna synthetase]]
+[[Category: Atp- binding]]
-[[Category: atp- binding]]
+[[Category: Class i aminoacyl- trna synthetase]]
-[[Category: class i aminoacyl- trna synthetase]]
+[[Category: Editing]]
-[[Category: editing]]
+[[Category: Ligase]]
-[[Category: ligase]]
+[[Category: Metal-binding]]
-[[Category: metal-binding]]
+[[Category: Nucleotide-binding zinc]]
-[[Category: nucleotide-binding zinc]]
+[[Category: Protein biosynthesis]]
-[[Category: protein biosynthesis]]
+[[Category: Synthetase]]
-[[Category: synthetase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 17:57:43 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:07:00 2008''