PMID- 10464285
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 36
DP  - 1999 Sep 3
TI  - The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases.
PG  - 25535-42
AB  - 2'-5'-Oligoadenylate (2-5(A)) synthetases are a family of interferon-induced
      enzymes that are activated by double-stranded RNA. To understand why, unlike
      other DNA and RNA polymerases, they catalyze 2'-5' instead of 3'-5'
      phosphodiester bond formation, we used molecular modeling to compare the
      structure of the catalytic domain of DNA polymerase beta (pol beta) to that of a 
      region of the P69 isozyme of 2-5(A) synthetase. Although the primary sequence
      identity is low, like pol beta, P69 can assume an alphabetabetaalphabetabetabeta 
      structure in this region. Moreover, mutation of the three Asp residues of P69,
      which correspond to the three catalytic site Asp residues of pol beta,
      inactivated the enzyme without affecting its substrate and activator binding
      capacity, providing further credence to the concept that this region is the
      catalytic domain of P69. This domain is highly conserved among all 2-5(A)
      synthetase isozymes. Biochemical and mutational studies demonstrated that
      dimerization of the P69 protein is required for its enzyme activity. However, a
      dimer containing a wild type subunit and an inactive catalytic domain mutant
      subunit was also active. The rate of catalysis of the heterodimer was half of
      that of the wild type homodimer, although the two proteins bound double-stranded 
      RNA and ATP equally well.
FAU - Sarkar, S N
AU  - Sarkar SN
AD  - Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic 
      Foundation, Cleveland, Ohio 44195, USA.
FAU - Ghosh, A
AU  - Ghosh A
FAU - Wang, H W
AU  - Wang HW
FAU - Sung, S S
AU  - Sung SS
FAU - Sen, G C
AU  - Sen GC
LA  - eng
GR  - CA-62220/CA/NCI NIH HHS/United States
GR  - CA-68782/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
SB  - IM
MH  - *2',5'-Oligoadenylate Synthetase/chemistry/genetics/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Catalysis
MH  - Dimerization
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
EDAT- 1999/08/28 00:00
MHDA- 1999/08/28 00:01
CRDT- 1999/08/28 00:00
PHST- 1999/08/28 00:00 [pubmed]
PHST- 1999/08/28 00:01 [medline]
PHST- 1999/08/28 00:00 [entrez]
AID - 10.1074/jbc.274.36.25535 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 3;274(36):25535-42. doi: 10.1074/jbc.274.36.25535.