PMID- 18979629
OWN - NLM
STAT- MEDLINE
DCOM- 20081201
LR  - 20081103
IS  - 1431-6730 (Print)
IS  - 1431-6730 (Linking)
VI  - 389
IP  - 8
DP  - 2008 Aug
TI  - Isoaspartate residues dramatically influence substrate recognition and turnover 
      by proteases.
PG  - 1043-53
LID - 10.1515/BC.2008.123 [doi]
AB  - Posttranslational modifications influence the structure, stability and biological 
      activity of proteins. Most of the reactions are enzyme-catalyzed, but some, such 
      as asparagine (Asn) and glutamine (Gln) deamidation and the isoaspartate (isoAsp) 
      formation within peptide chains, occur spontaneously. It has been previously 
      shown that certain peptide sequences form isoAsp quite fast if the Asp stretches 
      are exposed to the protein surface, thereby potentially changing susceptibility 
      to proteolysis at these sites. This tempted us to investigate the activity of 
      exo- and endopeptidases against Asp- or isoAsp-containing substrates. Members of 
      the prolyl oligopeptidase family were unable to cleave substrates after proline 
      if isoAsp was placed in the P2-position. Caspases, usually accepting Asp at 
      P1-position of their substrates, did not cleave isoAsp-containing sequences. 
      Similarly, the metal-dependent aminopeptidase amino peptidase N did not turnover 
      N-terminal isoAsp-containing substrates, nor could the endopeptidase matrix 
      metalloproteinase 3 (MMP 3) hydrolyze a serum amyloid A protein-like substrate if 
      the sequence contained isoAsp instead of Asp. Also, the highly specific 
      enterokinase, usually clipping after a stretch of four Asp residues and a lysine 
      in the P1 position, could not turnover substrates if the P2 amino acid was 
      replaced by isoAsp. In contrast, acylamino acid-releasing enzyme and dipeptidyl 
      peptidases 1, 2 and 4 hydrolyzed substrates containing the isoAsp-Ala motif.
FAU - Bohme, Livia
AU  - Bohme L
AD  - Probiodrug AG, Biocenter, Weinbergweg 22, D-06120 Halle/Saale, Germany.
FAU - Bar, Joachim Wolfgang
AU  - Bar JW
FAU - Hoffmann, Torsten
AU  - Hoffmann T
FAU - Manhart, Susanne
AU  - Manhart S
FAU - Ludwig, Hans-Henning
AU  - Ludwig HH
FAU - Rosche, Fred
AU  - Rosche F
FAU - Demuth, Hans-Ulrich
AU  - Demuth HU
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 0 (Isoaspartic Acid)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Enzyme Activation
MH  - Humans
MH  - Hydrolysis
MH  - Isoaspartic Acid/chemistry/*metabolism
MH  - Kinetics
MH  - Molecular Structure
MH  - Peptide Hydrolases/*metabolism
MH  - Substrate Specificity
EDAT- 2008/11/04 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/11/04 09:00
PHST- 2008/11/04 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/11/04 09:00 [entrez]
AID - 10.1515/BC.2008.123_bchm.just-accepted [pii]
AID - 10.1515/BC.2008.123 [doi]
PST - ppublish
SO  - Biol Chem. 2008 Aug;389(8):1043-53. doi: 10.1515/BC.2008.123.