2v0c: Difference between revisions

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Revision as of 05:07, 31 March 2008

File:2v0c.jpg

, resolution 1.85Å

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LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A SULPHAMOYL ANALOGUE OF LEUCYL-ADENYLATE IN THE SYNTHETIC SITE AND AN ADDUCT OF AMP WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) IN THE 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

2V0C is a Single protein structure of sequence 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 Mon Mar 31 05:06:59 2008

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

OCA

@@ Line 4: / Line 4: @@
 |PDB= 2v0c |SIZE=350|CAPTION= <scene name='initialview01'>2v0c</scene>, resolution 1.85&Aring;
 |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>
-|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=LEU:LEUCINE'>LEU</scene> and <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>
+|LIGAND= <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=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=LMS:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDRO-2-FURANYL]METHYL+SULFAMATE'>LMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
 |ACTIVITY=
 |GENE=
+|DOMAIN=
+|RELATEDENTRY=
+|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v0c OCA], [http://www.ebi.ac.uk/pdbsum/2v0c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2v0c RCSB]</span>
 }}
@@ Line 38: / Line 41: @@
 [[Category: Zhang, Y.]]
 [[Category: Zhou, H.]]
-[[Category: ANZ]]
-[[Category: LEU]]
-[[Category: SO4]]
-[[Category: ZN]]
 [[Category: aminoacyl-trna synthetase]]
 [[Category: atp + l-leucine + trna (leu) gives amp + ppi + l-leucyl-trna(leu)]]
@@ Line 52: / Line 51: @@
 [[Category: zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:52:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:06:59 2008''