2ZZB
Crystal structure of human thioredoxin reductase I and terpyridine platinum(II)
Summary for 2ZZB
| Entry DOI | 10.2210/pdb2zzb/pdb |
| Related | 2ZZ0 2ZZC |
| Descriptor | Thioredoxin reductase 1, cytoplasmic, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | rossmann fold, alternative splicing, cytoplasm, electron transport, fad, flavoprotein, nadp, nucleus, oxidoreductase, phosphoprotein, polymorphism, redox-active center, selenium, selenocysteine, transport |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm . Isoform 4: Cytoplasm. Isoform 5: Cytoplasm: Q16881 |
| Total number of polymer chains | 4 |
| Total formula weight | 230415.36 |
| Authors | Lo, Y.C.,Ko, T.P.,Wang, A.H.J. (deposition date: 2009-02-09, release date: 2009-08-18, Last modification date: 2024-10-30) |
| Primary citation | Lo, Y.C.,Ko, T.P.,Su, W.C.,Su, T.L.,Wang, A.H.J. Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1. J.Inorg.Biochem., 103:1082-1092, 2009 Cited by PubMed Abstract: Terpyridine-platinum(II) (TP-Pt(II)) complexes are known to possess DNA-intercalating activity and have been regarded as potential antitumor agents. However, their cytotoxic mechanism remains unclear. To investigate the possible mechanism, a series of TP-Pt(II) compounds were prepared and their biological activities assessed. The DNA binding activities of the aromatic thiolato[TP-Pt(II)] complexes were stronger than the aliphatic 2-hydroxylethanethiolato(2,2':6',2''-terpyridine)platinum(II) [TP(HET)]. TP-Pt(II) complexes inhibited topoisomerase IIalpha or topoisomerase I activity at IC(50) values of about 5 microM and 10-20 microM, respectively, whereas the human thioredoxin reductase 1 (hTrxR1) activity was inhibited with IC(50) values in the range of 58-78 nM. At the cellular level, they possessed cytotoxicity with IC(50) values between 7 and 19 microM against HeLa cells. Additionally, using X-ray crystallography and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, we elucidated that the TP-Pt(II) complexes inhibited hTrxR1 activity by blocking its C-terminal active-site selenocysteine. Therefore, TP-Pt(II) complexes possess inhibitory activities against multiple biological targets, and they may be further studied as anticancer agents. PubMed: 19525010DOI: 10.1016/j.jinorgbio.2009.05.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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