Abstract:
:In this study, we have mapped the intracellular alkylation sites of adozelesin and bizelesin, two potent analogs of CC-1065, in individual genes at the single-nucleotide level. Human colon carcinoma cells were treated with adozelesin and bizelesin, and the position of adducts were mapped within the PGK-1 and p53 genes by means of ligation-mediated polymerase chain reaction. The monofunctional alkylating agent adozelesin was found to alkylate genomic DNA predominantly within 5'-(A/T)(A/T)A* sequences. Additional sites of alkylation were observed within 5'-(A/T)(G/C)(A/T)A* sequences; however, these were considered to represent sites of medium to low preference. Bizelesin, a bifunctional analog capable of both DNA monofunctional alkylation and DNA interstrand cross-link formation, was also found to alkylate 5'-(A/T)(A/T)A* sequences. Putative bizelesin DNA interstrand cross-link sites indicated that AT-rich sequences are preferred in the intervening sequence between the two cross-linked adenines. Both six- and seven-nucleotide regions were identified as putative sites of DNA interstrand cross-link formation with 5'-TTTTTTA*, 5'-TTTATCA* and 5'-GTACTAA* sequences being preferred. Non-adenine bases are not observed as potential intracellular sites of either DNA interstrand cross-linking formation or monofunctional alkylation. Thus, the patterns of alkylation induced by adozelesin and bizelesin in genomic DNA are similar but not identical to that observed in purified cell-free DNA.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Lee CS,Pfeifer GP,Gibson NWdoi
10.1021/bi00185a043subject
Has Abstractpub_date
1994-05-17 00:00:00pages
6024-30issue
19eissn
0006-2960issn
1520-4995journal_volume
33pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Notwithstanding the relevance of their biological function, slow motions in proteins, beyond the microsecond range, are still poorly understood and often elusive. We propose that acrylamide quenching of Trp phosphorescence of deeply buried residues, when extended over the entire accessible range of lifetime measuremen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9009659
更新日期:2009-08-11 00:00:00
abstract::Tandem calponin-homology (CH) domains are the most common actin-binding domains in proteins. However, structural principles underlying their function are poorly understood. These tandem domains exist in multiple conformations with varying degrees of inter-CH-domain interactions. Dystrophin and utrophin tandem CH domai...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00741
更新日期:2015-09-08 00:00:00
abstract::Myosins are a superfamily of actin-binding motor proteins with significant variations in kinetic properties (such as actin binding affinity) between different isoforms. It remains unknown how such kinetic variations arise from the structural and dynamic tuning of the actin-myosin interface at the amino acid residue le...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi4006896
更新日期:2013-11-26 00:00:00
abstract::The substrate specificities of two incorrectly annotated enzymes belonging to cog3964 from the amidohydrolase superfamily were determined. This group of enzymes are currently misannotated as either dihydroorotases or adenine deaminases. Atu3266 from Agrobacterium tumefaciens C58 and Oant2987 from Ochrobactrum anthropi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi301483z
更新日期:2013-01-08 00:00:00
abstract::The effects of site-directed mutagenesis were used to explore the role of residues in M4 on the apparent Ki of a selective, K+-competitive inhibitor of the gastric H+,K+ ATPase, SCH28080. A double transfection expression system is described, utilizing HEK293 cells and separate plasmids encoding the alpha and beta subu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991837d
更新日期:2000-03-21 00:00:00
abstract::Beta2microglobulin (beta2m) is the major protein component of the fibrillar amyloid deposits isolated from patients diagnosed with dialysis-related amyloidosis (DRA). While investigating the molecular mechanism of amyloid fibril formation by beta2m, we found that the beta2m C-terminal peptide of 28 residues (cbeta2m) ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0301486
更新日期:2003-11-25 00:00:00
abstract::Fourier transform infrared (FTIR) spectroscopy was employed to examine the thermal denaturation of the Fe(III), Fe(II), and Fe(II)-CO forms of cytochrome c peroxidase and horseradish peroxidase in phosphate buffer at pD 7.0. The amide I' regions of the deconvolved spectra are consistent with predominantly alpha-helica...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952233m
更新日期:1996-04-30 00:00:00
abstract::The light chain of activated factor IX (FIXa) is involved in a number of functional properties, including FIXa enzymatic activity. This suggests the existence of a functional link between the FIXa light chain and the catalytic domain. The FIXa structure includes a few putative interactions between EGF2 and the proteas...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060451h
更新日期:2006-09-05 00:00:00
abstract::The conformational constraints for apoA-I bound to recombinant phospholipid complexes (rHDL) were attained from a combination of chemical cross-linking and mass spectrometry. Molecular distances were then used to refine models of lipid-bound apoA-I on both 80 and 96 A diameter rHDL particles. To obtain molecular const...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700384t
更新日期:2007-07-03 00:00:00
abstract::Transferrin exhibits heterogeneity in glycosylation characteristic of pathological changes in alcohol abuse and congenital disorders in glycosylation. This study investigated an alternative approach in the detection of carbohydrate-deficient transferrin based on the premise that glycosylation may afford some degree of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051749v
更新日期:2005-12-13 00:00:00
abstract::N-Acyl ethanolamines (NAEs) constitute a large and diverse class of signaling lipids that includes the endogenous cannabinoid anandamide. Like other lipid transmitters, NAEs are thought to be biosynthesized and degraded on-demand rather than being stored in vesicles prior to signaling. The identification of enzymes in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi060163l
更新日期:2006-04-18 00:00:00
abstract::G proteins play an important role in transmitting hormonal signals, and fluorescence techniques would be useful to study their cellular distribution and mechanisms. To prepare active fluorescent G protein Go/Gi or beta gamma subunits were reacted with fluorescein isothiocyanate (FITC) to label the alpha (F-alpha) and ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00060a035
更新日期:1993-03-09 00:00:00
abstract::A soluble extract prepared from cells of an Escherichia coli strain carrying the antibiotic resistance plasmid R6K is capable of carrying out the complete process of R6K DNA replication. DNA synthesis in vitro is dependent on the four deoxyribo- and ribonucleotide triphosphates and is sensitive to rifampin and strepto...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00606a017
更新日期:1978-06-27 00:00:00
abstract::Type II polyketides are a class of natural products that include pharmaceutically important aromatic compounds such as the antibiotic tetracycline and antitumor compound doxorubicin. The type II polyketide synthase (PKS) is a complex consisting of 5-10 standalone domains homologous to fatty acid synthase (FAS). Polyke...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi7016427
更新日期:2008-02-19 00:00:00
abstract::Specific interactions of human melanocortin-4 receptor (hMC4R) with its nonpeptide and peptide agonists were studied using alanine-scanning mutagenesis. The binding affinities and potencies of two synthetic, small-molecule agonists (THIQ, MB243) were strongly affected by substitutions in transmembrane alpha-helices (T...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0501840
更新日期:2005-08-30 00:00:00
abstract::To better understand origin recognition and initiation of DNA replication, we have examined by NMR complexes formed between the origin-binding domain of SV40 T antigen (T-ag-obd), the initiator protein of the SV40 virus, and cognate and noncognate DNA oligomers. The results reveal two structural effects associated wit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi030228+
更新日期:2004-06-08 00:00:00
abstract::Recent crystallographic data suggest that conserved residues in the connection subdomain and C-terminal ribonuclease H (RNase H) domain of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) contact the nascent DNA primer and modulate the trajectory of the template relative to the RNase H catalytic ce...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi015970t
更新日期:2002-04-16 00:00:00
abstract::The catalytic activity and inhibitor binding energetics of enzymes are often pH-dependent properties. Aspartic proteases comprise an important class of enzyme targets for structure-based drug design. We have performed a complete thermodynamic study of pepstatin binding to plasmepsin II, an aspartic proteinase found in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971550l
更新日期:1997-12-23 00:00:00
abstract::Animal galectins (lectins with specificity for beta-galactosides of glycan chains) are potent effectors in diverse aspects of cell sociology. Gene divergence has led to different groups and a marked interspecies variability in the number of members per group. Since the suitability of a model for studying functionality...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900083q
更新日期:2009-05-26 00:00:00
abstract::We have measured the rates and efficiencies of DNA unwinding (the number of ATP molecules hydrolyzed per DNA base pair unwound) catalyzed by the RecBC,RecBCD-K177Q (a site-directed mutant in the putative ATP-binding site in the RecD subunit), and RecBCD enzymes from Escherichia coli. The DNA unwinding rate was measure...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00198a022
更新日期:1994-08-16 00:00:00
abstract::Exoenzyme S (ExoS) is a mono-ADP-ribosyltransferase secreted by the opportunistic pathogen Pseudomonas aeruginosa. ExoS requires a eukaryotic factor, the 14-3-3 protein, for enzymatic activity. Here, two aspects of the activation of the ADP-ribosyltransferase activity of ExoS by 14-3-3 proteins are examined. Initial s...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991019l
更新日期:1999-09-14 00:00:00
abstract::Phosphorus-31 magic angle sample spinning NMR spectra have been employed to investigate the structure and composition of the mineral deposits in chicken bone. Three different pulse sequences, Bloch decay, cross-polarization, and dipolar suppression, were employed to obtain spectra from bone specimens of varying age. T...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00320a033
更新日期:1984-12-04 00:00:00
abstract::MRP1 (or ABCC1) is an ABC membrane protein that transports a wide range of natural products as well as glutathione (GSH)-, glucuronate-, and sulfate-conjugated metabolites. In addition, free GSH is required for MRP1 to transport several chemotherapeutic drugs. However, the mechanisms regulating the influence of GSH on...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0268807
更新日期:2003-03-25 00:00:00
abstract::The structures of hemes a and a3 of maize and wheat germ cytochrome c oxidase were investigated by resonance Raman spectroscopy. Comparison between the plant and mammalian cytochrome oxidases revealed that (i) the vinyl groups associated with hemes a and a3 vibrate at higher frequencies in the plant enzyme than in the...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00489a028
更新日期:1990-09-18 00:00:00
abstract::The effect of mutating Gly 478 to Ala in rat cytochrome P450 2B1 on the metabolism of N-benzyl-1-aminobenzotriazole was investigated. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of the wild-type enzyme was completely inactivated by incubating with 1 microM BBT. The G478A mutant, however, was not i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi971064y
更新日期:1997-09-30 00:00:00
abstract::Both the male and the female of Mastomys natalensis, an African rat, have high levels of nerve growth factor (NGF) in their submaxillary glands. Mastomys high molecular weight (HMW) NGF was purified by gel filtration and ion-exchange chromatography and was compared with HMW NGF from the male mouse submaxillary gland. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00418a007
更新日期:1988-09-06 00:00:00
abstract::AppA, a transcriptional antirepressor, regulates the steady expression of photosynthesis genes in Rhodobacter sphaeroides in response to high-intensity blue light and to redox signals. Its blue-light sensing is mediated by an N-terminal BLUF domain, a member of a novel flavin fold. The photocycle of this domain (AppA(...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi051367p
更新日期:2006-01-10 00:00:00
abstract::Sedimentation equilibrium and sedimentation velocity measurements demonstrate that turkey gizzard caldesmon is an elongated molecule of molecular mass 75 +/- 2 kDa. The frictional ratio (2.14) is consistent with a prolate ellipsoid of axial ratio 24, corresponding to an apparent length and width of 516 and 21.5 A, res...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00446a039
更新日期:1989-10-03 00:00:00
abstract::The UDP-glucuronosyltransferase (UGT) isozyme system is critical for protecting the body against endogenous and exogenous chemicals by linking glucuronic acid donated by UDP-glucuronic acid to a lipophilic acceptor substrate. UGTs convert metabolites, dietary constituents, and environmental toxicants to highly excreta...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8006127
更新日期:2008-07-15 00:00:00
abstract::Histidine-containing protein, HPr, is a phosphocarrier protein that is part of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated by enzyme I, and P-HPr transfers the phosphoryl group to the IIA domain of a number of sugar-specific enzyme II complexes. Autocatalytic phosphoryl tra...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00073a025
更新日期:1993-06-08 00:00:00