Document Detail


Activation of an Asp-124-->Asn mutant of haloalkane dehalogenase by hydrolytic deamidation of asparagine.
MedLine Citation:
PMID:  7828730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Haloalkane dehalogenase hydrolyses various 1-halo-n-alkanes to the corresponding alcohols by covalent catalysis with formation of an alkyl-enzyme intermediate. The carboxylate function of the nucleophilic aspartate (Asp-124) that displaces the halogen during formation of the intermediate was changed to an amide by site-directed mutagenesis (Asp-124-->Asn). Activity measurements and analysis of peptides containing the nucleophilic residue showed that the mutant enzyme was inactive, but that the activity increased by rapid deamidation of the asparagine residue, yielding wild type enzyme. There was no indication for isoaspartate formation during this process. The results suggest that a water molecule that is located close to the carboxyl function of Asp-124 in the X-ray structure is highly reactive and is responsible for the observed deamidation.
Authors:
F Pries; J Kingma; D B Janssen
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  FEBS letters     Volume:  358     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-02-23     Completed Date:  1995-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  171-4     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Groningen Biomolecular and Biotechnology Institute, University of Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Amides / chemistry
Amino Acid Sequence
Asparagine / metabolism*
Aspartic Acid / metabolism*
Base Sequence
DNA Primers
Deamination
Enzyme Activation
Hydrolases / genetics,  metabolism*
Hydrolysis
Molecular Sequence Data
Mutation
Point Mutation
Chemical
Reg. No./Substance:
0/Amides; 0/DNA Primers; 56-84-8/Aspartic Acid; 7006-34-0/Asparagine; EC 3.-/Hydrolases; EC 3.8.1.5/haloalkane dehalogenase

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