Document Detail


Kinetic analysis of three activated phenylalanyl intermediates generated by the initiation module PheATE of gramicidin S synthetase.
MedLine Citation:
PMID:  11330995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The three-domain initiation module PheATE (GrsA) of Bacillus brevis gramicidin S synthetase catalyzes the activation, thiolation and epimerization of L-phenylalanine (L-Phe), the first amino acid incorporated into the decapeptide antibiotic gramicidin S. There are three activated intermediates in the PheATE catalyzed chemical pathway: L-phenylalanyl-adenosine-5'-monophosphate diester (L-Phe-AMP), L-Phe-S-4'-phosphopantetheine(Ppant)- and D-Phe-S-4'-Ppant-acyl enzyme. In this study, we examined PheATE in single-turnover catalysis using rapid chemical quench techniques. Kinetic modeling of the process of disappearance of the substrate L-Phe, transient appearance and disappearance of L-Phe-AMP and the ad seriatim formation and equilibration of the L- and D-Phe-S-Ppant-acyl enzyme adducts allowed evaluation of the microscopic rate constants for the three chemical reactions in the initiation module PheATE. This study provides the first transient-state kinetic analysis of a nonribosomal peptide synthetase (NRPS) module.
Authors:
L Luo; C T Walsh
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  40     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-01     Completed Date:  2001-07-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5329-37     Citation Subset:  IM    
Affiliation:
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Monophosphate / analogs & derivatives,  metabolism
Alanine / genetics
Amino Acid Isomerases / genetics,  metabolism*
Amino Acid Motifs / genetics
Aminoacylation*
Apoenzymes / metabolism
Bacillus / enzymology,  genetics
Carbon Radioisotopes
Catalysis
Gramicidin / biosynthesis*
Histidine / genetics
Holoenzymes / genetics,  metabolism
Kinetics
Mutagenesis, Site-Directed
Pantetheine / analogs & derivatives*,  metabolism
Peptide Chain Initiation, Translational*
Phenylalanine / metabolism*
Protein Structure, Tertiary / genetics
Grant Support
ID/Acronym/Agency:
GM20011/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Apoenzymes; 0/Carbon Radioisotopes; 0/Holoenzymes; 0/phenylalanyl-AMP anhydride; 1405-97-6/Gramicidin; 2226-71-3/4'-phosphopantetheine; 496-65-1/Pantetheine; 56-41-7/Alanine; 61-19-8/Adenosine Monophosphate; 63-91-2/Phenylalanine; 71-00-1/Histidine; EC 5.1.1.-/Amino Acid Isomerases; EC 5.1.1.11/phenylalanine racemase (ATP-hydrolyzing)

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


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