Document Detail


Crystal structures of phenylalanyl-tRNA synthetase complexed with phenylalanine and a phenylalanyl-adenylate analogue.
MedLine Citation:
PMID:  10092459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The crystal structures of Thermus thermophilus phenylalanyl-tRNA synthetase (PheRS) complexed with phenylalanine and phenylalaninyl-adenylate (PheOH-AMP), the synthetic analogue of phenylalanyl-adenylate, have been determined at 2.7A and 2.5A resolution, respectively. Both Phe and PheOH-AMP are engulfed in the active site cleft of the catalytic alpha-subunit of PheRS, and neither makes contact with the PheRS beta-subunit. The conformations and binding of Phe are almost identical in both complexes. The recognition of Phe by PheRS is achieved through a mixture of multiple van der Waals interactions and hydrogen bonds. The side-chain of the Phe substrate is sandwiched between the hydrophobic side-chains of Phealpha258 and Phealpha260 on one side, and the main-chain atoms of the two adjacent beta-strands on the other. The side-chains of Valalpha261 and Alaalpha314 form the back wall of the amino acid binding pocket. In addition, PheRS residues (Trpalpha149, Seralpha180, Hisalpha178, Argalpha204, Glnalpha218, and Glualpha220) form a total of seven hydrogen bonds with the main-chain atoms of Phe. The conformation of PheOH-AMP and the network of interactions of its AMP moiety with PheRS are reminiscent of the other class II synthetases. The structural similarity between PheRS and histidyl-tRNA synthetase extends to the amino acid binding site, which is normally unique for each enzyme. The complex structures suggest that the PheRS beta-subunit may affect the first step of the reaction (formation of phenylalanyl-adenylate) through the metal-mediated conserved alpha/beta-subunit interface. The modeling of tyrosine in the active site of PheRS revealed no apparent close contacts between tyrosine and the PheRS residues. This result implies that the proofreading mechanism against activated tyrosine, rather than direct recognition, may play the major role in the PheRS specificity.
Authors:
L Reshetnikova; N Moor; O Lavrik; D G Vassylyev
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of molecular biology     Volume:  287     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-06-07     Completed Date:  1999-06-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  555-68     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Affiliation:
Institute of Molecular Biology, Moscow, 117984, Russia.
Data Bank Information
Bank Name/Acc. No.:
PDB/1B70;  1B7Y
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MeSH Terms
Descriptor/Qualifier:
Adenosine Monophosphate / analogs & derivatives*,  chemistry
Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Macromolecular Substances
Metals / chemistry
Models, Molecular
Molecular Sequence Data
Phenylalanine / chemistry*
Phenylalanine-tRNA Ligase / chemistry*,  genetics,  metabolism
Protein Conformation
Sequence Homology, Amino Acid
Thermus thermophilus / enzymology,  genetics
Chemical
Reg. No./Substance:
0/Macromolecular Substances; 0/Metals; 35874-27-2/phenylalanyl adenylate; 61-19-8/Adenosine Monophosphate; 63-91-2/Phenylalanine; EC 6.1.1.20/Phenylalanine-tRNA Ligase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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