N6-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

被引:17
作者
Amiable, Claire [1 ,2 ,3 ]
Pochet, Sylvie [1 ,2 ]
Padilla, Andre [4 ,5 ,6 ]
Labesse, Gilles [4 ,5 ,6 ]
Kaminski, Pierre Alexandre [1 ,2 ]
机构
[1] Inst Pasteur, Unite Chim & Biocatalyse, Paris, France
[2] CNRS, UMR3523, Paris, France
[3] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[4] CNRS, Ctr Biochim Structurale, UMR5048, Montpellier, France
[5] INSERM, U554, Montpellier, France
[6] Univ Montpellier 1 & 2, IFR3, Montpellier, France
来源
PLOS ONE | 2013年 / 8卷 / 11期
关键词
BREAST-CANCER CELLS; KINETIN-RIBOSIDE; LACTATE-DEHYDROGENASE; ANTICANCER ACTIVITY; HL-60; CELLS; RCL; APOPTOSIS; GENE; NUCLEOSIDE; ANALOGS;
D O I
10.1371/journal.pone.0080755
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2'-deoxyribonucleoside 5'-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N-6-substituted AMPs, and among them, cytotoxic cytokinin riboside 5'-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth.
引用
收藏
页数:11
相关论文
共 41 条
  • [1] BIOCHEMICAL PROPERTIES OF NUCLEOSIDE OF 3-AMINO-1,5-DIHYDRO-5-METHYL-1,4,5,6,8-PENTAAZAACENAPHTHYLENE (NSC-154020)
    BENNETT, LL
    SMITHERS, D
    HILL, DL
    ROSE, LM
    ALEXANDER, JA
    [J]. BIOCHEMICAL PHARMACOLOGY, 1978, 27 (02) : 233 - 241
  • [2] The experimental chemotherapeutic N6-furfuryladenosine (kinetin-riboside) induces rapid ATP depletion, genotoxic stress, and CDKN1A (p21) upregulation in human cancer cell lines
    Cabello, Christopher M.
    Bair, Warner B., III
    Ley, Stephanie
    Lamore, Sarah D.
    Azimian, Sara
    Wondrak, Georg T.
    [J]. BIOCHEMICAL PHARMACOLOGY, 2009, 77 (07) : 1125 - 1138
  • [3] Inhibitory effect of kinetin riboside in human heptamoa, HepG2
    Cheong, Jane
    Goh, David
    Yong, Jean Wan Hong
    Tan, Swee Ngin
    Ong, Eng Shi
    [J]. MOLECULAR BIOSYSTEMS, 2009, 5 (01) : 91 - 98
  • [4] Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells
    Choi, Bo-Hwa
    Kim, Wanil
    Wang, Qiuxia Chelsia
    Kim, Dong-Chan
    Tan, Swee Ngin
    Yong, Jean Wan Hing
    Kim, Kyong-Tai
    Yoon, Ho Sup
    [J]. CANCER LETTERS, 2008, 261 (01) : 37 - 45
  • [5] Solution Structure of RCL, a Novel 2′-Deoxyribonucleoside 5′-Monophosphate N-glycosidase
    Doddapaneni, Kiran
    Mahler, Bryon
    Pavlovicz, Ryan
    Haushalter, Adam
    Yuan, Chunhua
    Wu, Zhengrong
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2009, 394 (03) : 423 - 434
  • [6] Preparation, biological activity and endogenous occurrence of N6-benzyladenosines
    Dolezal, Karel
    Popa, Igor
    Hauserova, Eva
    Spichal, Lukas
    Chakrabarty, Kuheli
    Novak, Ondrej
    Krystof, Vladimir
    Voller, Jiri
    Holub, Jan
    Strnad, Miroslav
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (11) : 3737 - 3747
  • [7] Effects of Kinetin Riboside on Proliferation and Proapoptotic Activities in Human Normal and Cancer Cell Lines
    Dudzik, Paulina
    Dulinska-Litewka, Joanna
    Wyszko, Eliza
    Jedrychowska, Patrycja
    Opalka, Maciej
    Barciszewski, Jan
    Laidler, Piotr
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2011, 112 (08) : 2115 - 2124
  • [8] Probing the Active Site of the Deoxynucleotide N-Hydrolase Rcl Encoded by the Rat Gene c6orf108
    Dupouy, Christelle
    Zhang, Chi
    Padilla, Andre
    Pochet, Sylvie
    Kaminski, Pierre Alexandre
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (53) : 41806 - 41814
  • [9] Coot:: model-building tools for molecular graphics
    Emsley, P
    Cowtan, K
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 : 2126 - 2132
  • [10] SOME SHORT-CHAIN N6-SUBSTITUTED ADENOSINE-ANALOGS WITH ANTI-TUMOR PROPERTIES
    FLEYSHER, MH
    BERNACKI, RJ
    BULLARD, GA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (12) : 1448 - 1452