PMID- 10608900
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Functional significance of the conserved residues for the 23-residue module among
      MTH1 and MutT family proteins.
PG  - 38251-9
AB  - Human MTH1 and Escherichia coli MutT proteins hydrolyze 7, 8-dihydro-8-oxo-dGTP
      (8-oxo-dGTP) to monophosphate, thus avoiding the incorporation of
      8-oxo-7,8-dihydroguanine into nascent DNA. Although only 30 amino acid residues
      (23%) are identical between MTH1 and MutT, there is a highly conserved region
      consisting of 23 residues (MTH1, Gly(36)-Gly(58)) with 14 identical residues. A
      chimeric protein MTH1-Ec, in which the 23-residue sequence of MTH1 was replaced
      with that of MutT, retains its capability to hydrolyze 8-oxo-dGTP, thereby
      indicating that the 23-residue sequences of MTH1 and MutT are functionally and
      structurally equivalent and constitute functional modules. By saturation
      mutagenesis of the module in MTH1, 14 of the 23 residues proved to be essential
      to exert 8-oxo-dGTPase activity. For the other 9 residues (40, 42, 44, 46, 47,
      49, 50, 54, and 58), positive mutants were obtained, and Arg(50) can be replaced 
      with hydrophobic residues (Val, Leu, or Ile), with a greater stability and higher
      specific activity of the enzyme. Indispensabilities of Val(39), Ile(45), and
      Leu(53) indicate that an amphipathic property of alpha-helix I consisting of 14
      residues of the module (Thr(44)-Gly(58)) is essential to maintain the stable
      catalytic surface for 8-oxo-dGTPase.
FAU - Fujii, Y
AU  - Fujii Y
AD  - Department of Biochemistry, Medical Institute of Bioregulation, Kyushu
      University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Shimokawa, H
AU  - Shimokawa H
FAU - Sekiguchi, M
AU  - Sekiguchi M
FAU - Nakabeppu, Y
AU  - Nakabeppu Y
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Bacterial Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (MTH1 protein, S cerevisiae)
RN  - 0 (Membrane Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - EC 3.6.1.- (mutT protein, E coli)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bacterial Proteins/chemistry/genetics/*metabolism
MH  - Base Sequence
MH  - Conserved Sequence
MH  - DNA Primers
MH  - DNA, Complementary
MH  - Escherichia coli/metabolism
MH  - *Escherichia coli Proteins
MH  - Fungal Proteins/chemistry/genetics/*metabolism
MH  - Humans
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Phosphoric Monoester Hydrolases/chemistry/genetics/*metabolism
MH  - Pyrophosphatases
MH  - *Saccharomyces cerevisiae Proteins
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.38251 [doi]
AID - S0021-9258(19)53020-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):38251-9. doi: 10.1074/jbc.274.53.38251.