PMID- 10373420
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1
      protein.
PG  - 18201-5
AB  - The possibility that Escherichia coli MutT and human MTH1 (hMTH1) hydrolyze
      oxidized DNA precursors other than 8-hydroxy-dGTP (8-OH-dGTP) was investigated.
      We report here that hMTH1 hydrolyzed 2-hydroxy-dATP (2-OH-dATP) and
      8-hydroxy-dATP (8-OH-dATP), oxidized forms of dATP, but not (R)-8,5'-cyclo-dATP, 
      5-hydroxy-dCTP, and 5-formyl-dUTP. The kinetic parameters indicated that
      2-OH-dATP was hydrolyzed more efficiently and with higher affinity than
      8-OH-dGTP. 8-OH-dATP was hydrolyzed as efficiently as 8-OH-dGTP. The preferential
      hydrolysis of 2-OH-dATP over 8-OH-dGTP was observed at all of the pH values
      tested (pH 7.2 to pH 8.8). In particular, a 5-fold difference in the hydrolysis
      efficiencies for 2-OH-dATP over 8-OH-dGTP was found at pH 7.2. However, E. coli
      MutT had no hydrolysis activity for either 2-OH-dATP or 8-OH-dATP. Thus, E. coli 
      MutT is an imperfect counterpart for hMTH1. Furthermore, we found that
      2-hydroxy-dADP and 8-hydroxy-dGDP competitively inhibited both the 2-OH-dATP
      hydrolase and 8-OH-dGTP hydrolase activities of hMTH1. The inhibitory effects of 
      2-hydroxy-dADP were 3-fold stronger than those of 8-hydroxy-dGDP. These results
      suggest that the three damaged nucleotides share the same recognition site of
      hMTH1 and that it is a more important sanitization enzyme than expected thus far.
FAU - Fujikawa, K
AU  - Fujikawa K
AD  - Department of Environmental Oncology, Institute of Industrial Ecological
      Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka,
      Yahatanishi-ku, Kitakyushu 807-8555, Japan.
FAU - Kamiya, H
AU  - Kamiya H
FAU - Yakushiji, H
AU  - Yakushiji H
FAU - Fujii, Y
AU  - Fujii Y
FAU - Nakabeppu, Y
AU  - Nakabeppu Y
FAU - Kasai, H
AU  - Kasai H
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 (Bacterial Proteins)
RN  - 0 (Deoxyadenine Nucleotides)
RN  - 0 (Escherichia coli 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)
RN  - EC 3.6.1.55 (8-oxodGTPase)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - K8KCC8SH6N (2'-deoxyadenosine triphosphate)
SB  - IM
MH  - Bacterial Proteins/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - *DNA Repair Enzymes
MH  - Deoxyadenine Nucleotides/*metabolism
MH  - Escherichia coli
MH  - *Escherichia coli Proteins
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Oxidation-Reduction
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Pyrophosphatases
MH  - Substrate Specificity
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18201 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18201-5. doi: 10.1074/jbc.274.26.18201.