PMID- 9756878
OWN - NLM
STAT- MEDLINE
DCOM- 19981102
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 41
DP  - 1998 Oct 9
TI  - Autoprocessing and peptide substrates for human herpesvirus 6 proteinase.
PG  - 26441-6
AB  - Autoprocessing of the precursor form of human herpesvirus 6 (HHV-6) proteinase at 
      two sites (termed M and R) is required to generate the mature enzyme. Kinetic 
      constants were determined for the hydrolysis of a series of synthetic peptide 
      substrates by mature HHV-6 proteinase, purified to homogeneity. Truncation or 
      replacement of individual residues in peptides mimicking the R-site sequence, 
      indicated that the minimum length for effective hydrolysis by the viral enzyme 
      was P4-P3-P2-Ala*Ser-P2'-P3'-P4' and revealed the importance of the P1 Ala and P4 
      Tyr residues. Consequently, relevant (P1 or P4) mutations were introduced into 
      the precursor form of the proteinase and the ability of these altered proteins to 
      autoprocess was examined. Introduction of Val in place of the P1 Ala at the 
      M-site essentially abrogated cleavage but mature HHV-6 proteinase was still 
      generated by cleavage at the R-site, indicating that processing of the M-site is 
      not a prerequisite for cleavage of the R-site in the precursor. At the R-site, 
      mutation of the P1 Ala, or of the preceding P4 Tyr residue, prevented processing 
      at the R-site in the precursor so that the mature form of HHV-6 proteinase was 
      not generated. The accumulated data suggest a possible new approach to the design 
      of inhibitors for therapeutic intervention in the life cycle of herpesviruses.
FAU - Tigue, N J
AU  - Tigue NJ
AD  - School of Molecular and Medical Biosciences, University of Wales, P. O. Box 911, 
      Cardiff CF1 3US, Wales, United Kingdom.
FAU - Kay, J
AU  - Kay J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Peptides)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - DNA Primers
MH  - Endopeptidases/*metabolism
MH  - Enzyme Precursors/genetics/*metabolism
MH  - Herpesvirus 6, Human/*enzymology
MH  - Hydrolysis
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Peptides/*metabolism
MH  - *Protein Processing, Post-Translational
MH  - Sequence Deletion
MH  - Substrate Specificity
EDAT- 1998/10/03 00:00
MHDA- 1998/10/03 00:01
CRDT- 1998/10/03 00:00
PHST- 1998/10/03 00:00 [pubmed]
PHST- 1998/10/03 00:01 [medline]
PHST- 1998/10/03 00:00 [entrez]
AID - S0021-9258(19)59768-X [pii]
AID - 10.1074/jbc.273.41.26441 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Oct 9;273(41):26441-6. doi: 10.1074/jbc.273.41.26441.