Abstract:
:The purpose of this study was to investigate the molecular action of lithocholic acid (LCA), known as a selective inhibitor of DNA polymerase beta (pol beta). The 39-kDa pol beta was separated proteolytically into two fragments of the template-primer binding domain (8 kDa) and the catalytic domain (31 kDa). LCA bound tightly to the 8-kDa fragment but not to the 31-kDa fragment. We examined the structural interaction with the 8-kDa domain using LCA. On (1)H-(15)N HMQC NMR analysis of pol beta with LCA, the 8-kDa domain bound to LCA as a 1:1 complex with a dissociation constant (K(D)) of 1.56 mM. The chemical shifts were observed only in residues mainly in helix-3, helix-4, and the 79-87 turn of the same face. No significant shifts were observed for helix-1, helix-2, and other loops of the 8-kDa domain. This region was composed mainly of three amino acid residues (Lys60, Leu77, and Thr79) of pol beta on the LCA interaction interface. The inhibition mechanism and the structure-function relationship between pol beta and LCA is discussed.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Mizushina Y,Ohkubo T,Sugawara F,Sakaguchi Kdoi
10.1021/bi001276msubject
Has Abstractpub_date
2000-10-17 00:00:00pages
12606-13issue
41eissn
0006-2960issn
1520-4995pii
bi001276mjournal_volume
39pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The zinc-dependent metallo-beta-lactamases are a group of bacterial enzymes that pose a threat to the future efficacy of present-day antibiotics. Their mechanism is poorly understood, and there are no clinically useful inhibitors. While most members of the group contain two tightly bound zinc ions in their active site...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047709t
更新日期:2005-03-29 00:00:00
abstract::Complete 1H NMR sequential assignments have been made for copper(I)- and silver (I)-substituted metallothionein (MT) from Saccharomyces cerevisiae using standard 2D 1H NMR methods. The fingerprint region of the COSY spectrum of both metalloproteins shows a doubling of a few backbone proton resonances from residue K41 ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00077a032
更新日期:1993-07-06 00:00:00
abstract::BtuB is a TonB-dependent transport protein that binds and carries vitamin B(12) across the outer membrane of Gram negative bacteria such as Escherichia coli. Previous work has demonstrated that the Ton box, a highly conserved segment near the N-terminus of the protein, undergoes an order-to-disorder transition upon th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061051x
更新日期:2006-09-12 00:00:00
abstract::To study the effects of methylation damage on DNA replication in vitro, the plasmid pSVori containing the SV40 origin of replication was reacted with N-methyl-N-nitrosourea and used as a substrate for SV40 T antigen dependent replication by HeLa cell extracts. The plasmid was methylated with a range of N-methyl-N-nitr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00212a035
更新日期:1993-12-14 00:00:00
abstract::The packing of lipids into different aggregates, such as spheres, rods, or bilayers, is dependent on the hydrophobic volume, the hydrocarbon-water interfacial area, and the hydrocarbon chain length of the participating molecules, according to the self-assembly theory [Israelachvili, J. N., Marcelja, S., & Horn, R. G. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00371a038
更新日期:1986-11-18 00:00:00
abstract::The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF-50 binding. The crystal structure of the B...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801115g
更新日期:2008-11-04 00:00:00
abstract::TP40 is a chimeric protein containing transforming growth factor alpha (TGF-alpha) at the N-terminus and a derivative of a 40,000-Da segment (PE40 delta cys) of Pseudomonas exotoxin (PE). PE40 delta cys contains domains Ib, II, and III of PE in which the cysteines are mutated to alanines. The rationale for inclusion o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00064a037
更新日期:1993-04-06 00:00:00
abstract::Two-dimensional nuclear magnetic resonance techniques were used to assign the NH, C alpha H, and C beta H protons of over 60 of the 104 amino acid residues in the 1H NMR spectrum of horse ferrocytochrome c. The majority of these amino acids were completely assigned. Assignments were based on the analysis of two-dimens...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00341a002
更新日期:1985-09-24 00:00:00
abstract::The Gbeta and Ggamma subunit of the heterotrimeric G proteins form a functional dimer that is stable once assembled in vivo or in vitro. The requirements, mechanism, and specificity of dimer formation are still incompletely understood, but represent important biochemical processes involved in the specificity of cellul...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0504254
更新日期:2005-09-06 00:00:00
abstract::Secondary structure in RNA targets is a significant barrier to short DNA probes. However, when such targets are the end product of an in vitro amplification scheme, it is possible to carry out transcription in the presence of nucleoside triphosphate analogues that reduce secondary structure of the RNA without impairin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049196w
更新日期:2004-08-10 00:00:00
abstract::The oxygen transfer to p-hydroxybenzoate catalyzed by p-hydroxybenzoate hydroxylase (PHBH) has been shown to occur via a C4a-hydroperoxide of the flavin. Two factors are likely to be important in facilitating the transfer of oxygen from the C4a-hydroperoxide to the substrate. (a) The positive electrostatic potential o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010892v
更新日期:2001-07-31 00:00:00
abstract::In the anaerobic sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough (DvH), the genome sequencing revealed the presence of three operons encoding formate dehydrogenases. fdh1 encodes an alphabetagamma trimeric enzyme containing 11 heme binding sites; fdh2 corresponds to an alphabetagamma trimeric enzyme wi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0515366
更新日期:2005-11-15 00:00:00
abstract::Structurally diverse small molecules, including 5-(2-benzofuryl)-4-phenyl-1,2,4-triazole-3-thiol (BETT), have been identified via high-throughput screening as activators of caspase-3 in HeLa cell extracts. However, little is known about their mechanism of action. In this study, we investigate how BETT regulates prothy...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9022329
更新日期:2010-03-09 00:00:00
abstract::Despite the high degree of sequence similarity in their basic-helix-loop-helix (BHLH) domains, MASH-1 and MyoD are involved in different biological processes. In order to define possible differences between the DNA binding specificities of these two proteins, we investigated the DNA binding properties of MASH-1 by cir...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00035a008
更新日期:1995-09-05 00:00:00
abstract::The flavin-dependent quiescin-sulfhydryl oxidase (QSOX) inserts disulfide bridges into unfolded reduced proteins with the reduction of molecular oxygen to form hydrogen peroxide. This work investigates how QSOX and protein disulfide isomerase (PDI) cooperate in vitro to generate native pairings in two unfolded reduced...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801604x
更新日期:2008-11-18 00:00:00
abstract::Biochemical properties of a detergent-solubilized tetrodotoxin binding component from Electrophorus electricus have been examined and compared with those found for the membrane-bound protein. The toxin binding component was solubilized with high efficiency by a variety of nonionic detergents and with lower efficiency ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00267a029
更新日期:1982-11-23 00:00:00
abstract::Biochemical experiments, using the well-defined human liver CYP2C9 expressed in yeast, and molecular modeling techniques were used to derive a predictive model for substrates of CYP2C9. The ability of 10 2-aroylthiophenes related to tienilic acid to act as substrates for CYP2C9 was studied. Four of them were original ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00033a007
更新日期:1995-08-22 00:00:00
abstract::The human translin protein binds a variety of sequences (chromosomal breakpoint consensus sequences, their sequence variants, as well as nonbreakpoint sequences such as simple AT and GC repeats) at nanomolar protein concentration when short single strands ( approximately 20-30mers) are used as DNA targets. The protein...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi026378m
更新日期:2002-12-24 00:00:00
abstract::ISU-type proteins mediate cluster transfer to apo protein targets. Rate constants have been determined for cluster transfer from ISU to apo Fd for both Homo sapiens and Schizosaccharomyces pombe proteins, and cross reactions have also been examined. Substitution of a key aspartate residue of ISU is found to decrease t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0256781
更新日期:2002-07-16 00:00:00
abstract::The development of inhibitors of insulin-regulated aminopeptidase (IRAP), a membrane-bound zinc metallopeptidase, is a promising approach for the discovery of drugs for the treatment of memory loss such as that associated with Alzheimer's disease. There is, however, no consensus in the literature about the mechanism b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101893w
更新日期:2011-04-05 00:00:00
abstract::Elastin binding proteins from plasma membranes of elastin-producing cells were isolated by affinity chromatography on immobilized elastin peptides. Three proteins of 67, 61, and 55 kDa were released from the elastin resin by guanidine/detergent, soluble elastin peptides, synthetic peptide VGVAPG, or galactoside sugars...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00435a014
更新日期:1989-05-02 00:00:00
abstract::Murine epidermal growth factor (EGF), a 53 amino acid protein, has been modified by enzymic digestion, site-specific chemical reactions, and recombinant DNA technology. After trypsin digestion the EGF derivatives EGF1-48 (called EGF-T) and EGF1-45 (called EGF-T2) were separated from the residual EGF and the C-terminal...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00414a005
更新日期:1988-07-12 00:00:00
abstract::Fluorometric titrations of papain, succinyl-papain, and the corresponding methylthio derivatives of Cys-25 (papain-S-SCH3 and succinyl-papain-S-SCH3) were determined. Removal of the methylthio group from Cys-25 resulted in an increase of approximately 4 pK units in the fluorometrically determined pK value. The corresp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00504a600
更新日期:1981-01-06 00:00:00
abstract::We studied the binding of peptides containing five basic residues to membranes containing acidic lipids. The peptides have five arginine or lysine residues and zero, one, or two alanines between the basic groups. The vesicles were formed from mixtures of a zwitterionic lipid, phosphatidylcholine, and an acidic lipid, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00121a026
更新日期:1992-02-18 00:00:00
abstract::The structure of the dimeric form of the protein L7/L12 from ribosomes from Escherichia coli was studied by using the heterobifunctional cross-linker 4-(6-formyl-3-azidophenoxy)butyrimidate. The imidate group of the cross-linker reacts very specifically with Lys-51 of L7/L12. Subsequent cross-linking of this modified ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00507a057
更新日期:1981-02-17 00:00:00
abstract::Human liver aldehyde dehydrogenase isozymes E1 and E2 (EC 1.2.1.3) are both completely and irreversibly inactivated by bromoacetophenone (2-bromo-1-phenylethanone). Steady-state kinetics with both acetophenone and chloroacetophenone indicated interaction with the same enzyme form as the aldehyde substrate. Saturation ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00366a030
更新日期:1986-09-09 00:00:00
abstract::A stable green heme was extracted from ferric cyanosulfmyoglobin after it had undergone an internal conversion reaction. After iron removal and conversion to the methyl ester, the resulting green porphyrin was purified by high-pressure liquid chromatography. Visible, 1H NMR, and mass spectrometric studies provided evi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00374a021
更新日期:1986-12-30 00:00:00
abstract::Protein phosphatase-1 (PP1) is an essential protein Ser/Thr phosphatase that is extraordinarily conserved from yeast to human, and Inhibitor-2 (I-2) is the most ancient of the heat-stable proteins specific for PP1. We identified novel I-2 homologues in Caenorhabditis elegans (Ce) and Xenopus laevis (Xe) and compared t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602369m
更新日期:2007-03-06 00:00:00
abstract::Our recently reported pressure-jump relaxation kinetics experiments on staphylococcal nuclease folding and unfolding [Vidugiris et al. (1995) Biochemistry 34, 4909] demonstrated that both transitions exhibit positive activation volumes, with that of folding being much larger than that of unfolding. Thus high pressure ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952012g
更新日期:1996-03-26 00:00:00
abstract::Nephrocalcin (NC), a calcium-binding glycoprotein of 14,000 molecular weight as a monomer, is known to inhibit the growth of calcium oxalate monohydrate (COM) crystals in renal tubules. We have isolated NC from bovine kidney tissue and purified into four isoforms, fractions A-D. NC-A and NC-B strongly inhibit the grow...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi961200j
更新日期:1996-11-26 00:00:00