Document Detail

Molecular ruler of tripeptidylpeptidase II: Mechanistic principle of exopeptidase selectivity.
MedLine Citation:
PMID:  21946061     Owner:  NLM     Status:  Publisher    
The structure of tripeptidylpeptidase II (TPPII) has shown that it belongs to the group of exopeptidases which use a double-Glu motif to convey aminopeptidase activity. TPPII has been implicated in vital biological processes. At least one of these, antigen processing, requires the involvement of its endopeptidase activity. In order to understand the extent and molecular basis of this unusual functional promiscuity we have performed a systematic kinetic analysis of wild type Drosophila melanogaster TPPII and five point mutants of the double-Glu-motif (E312/E343) involving natural substrates. Unlike the known double-Glu motives of other exopeptidases, the double-Glu motif of TPPII is distinctly asymmetrical: E-312 is the crucial determinant of the aminotripeptidolytic ruler mechanism. It both blocks the active-site cleft at substrate position P4 and forms a salt bridge with the N-terminus of the substrate. In contrast, E343 forms a much weaker salt bridge than E-312 and it does not have a blocking role. An endopeptidase substrate can bind at relatively high affinity if the length of the substrate permits binding to several S' sites. However, the lacking alignment of the substrate by the double-Glu motif causes the endopeptidolytic K(cat)/K(M) of TPPII to be very low.
Jürgen Peters; Anne-Marie Schönegge; Beate Rockel; Wolfgang Baumeister
Publication Detail:
Type:  -     Date:  2011-9-16
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Max-Planck-Institute of Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152 Martinsried, Germany.
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