Abstract:
:Voltage-dependent anion channel 1 (VDAC1) situated in the outer mitochondrial membrane regulates the transfer of various metabolites and is a key player in mitochondria-mediated apoptosis. Although many small chemicals that modulate the functions of VDAC1 have been reported to date, most, if not all, of them cannot be regarded as specific reagents due to their interactions with other transporters or enzymes. By screening our chemical libraries using isolated Saccharomyces cerevisiae mitochondria, we found pentenediol (PTD)-type compounds (e.g., PTD-023) as new specific inhibitors of VDAC1. PTD-023 inhibited overall ADP-uptake/ATP-release reactions in isolated mitochondria at a single digit μM level. To identify the binding position of PTDs in VDAC1 by visualizing PTD-bound peptides, we conducted ligand-directed tosyl (LDT) chemistry using the synthetic LDT reagent t-PTD-023 derived from the parent PTD-023 in combination with mutagenesis experiments. t-PTD-023 made a covalent bond predominantly and subsidiarily with nucleophilic Cys210 and Cys130, respectively, indicating that PTDs bind to the region interactive with both residues. Site-directed mutations of hydrogen bond-acceptable Asp139 and Glu152 to Ala, which were selected as potential interactive partners of the critical pentenediol moiety based on the presumed binding model of PTDs in VDAC1, resulted in a decrease in susceptibility against PTD-023. This result strongly suggests that PTDs bind to VDAC1 through a specific hydrogen bond with the two residues. The present study is the first to demonstrate the binding position of specific inhibitors of VDAC1 at the amino acid level.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Unten Y,Murai M,Yamamoto T,Watanabe A,Ichimaru N,Aburaya S,Aoki W,Shinohara Y,Miyoshi Hdoi
10.1021/acs.biochem.8b01209subject
Has Abstractpub_date
2019-02-26 00:00:00pages
1141-1154issue
8eissn
0006-2960issn
1520-4995journal_volume
58pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::A 15-residue fragment within the major continuous domain of gp120 from HIV-1 that can bind independently to the CD4 receptor has been shown to have the property of behaving as a solvent polarity-dependent conformational switch. The switch behavior (cooperative transition from beta-sheet to helical conformation as a fu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi952045w
更新日期:1996-01-16 00:00:00
abstract::The trimeric main light-harvesting complex (LHC-II) is the only antenna complex of higher plants of which a high-resolution 3D structure has been obtained (Kühlbrandt, W., Wang, D., and Fujiyoshi, Y. (1994) Nature 367, 614-621) and which can be refolded in vitro from its components. Four different recombinant forms of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi015875k
更新日期:2002-02-19 00:00:00
abstract::The potency of cholesterol to affect the acyl chain order and dynamics of cardiolipin membranes in the liquid-crystalline state was monitored by steady-state and time-resolved fluorescence anisotropy as well as excited-state lifetime measurements with cis- and trans-parinaric acids as probes. Up to a cholesterol mole ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00357a054
更新日期:1986-05-06 00:00:00
abstract::Incubation of bovine plasma amine oxidase (BPAO) with benzylamine and various p-substituted analogues results in a time-dependent inactivation that is attributable to buildup of the H(2)O(2)-turnover product on the basis of protection afforded by coincubation with catalase. The mechanism of inactivation is distinct fr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002118y
更新日期:2001-01-23 00:00:00
abstract::CHO cells expressing the human insulin receptors (IR) were used to evaluate the effect of the potent farnesyltransferase inhibitor, manumycin, on insulin antiapoptotic function. Cell treatment with manumycin blocked insulin's ability to suppress pro-apoptotic caspase-3 activity which led to time-dependent proteolytic ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000995y
更新日期:2000-10-17 00:00:00
abstract::Miniproteins reduce the complexity of the protein-folding problem allowing systematic studies of contributions to protein folding and stabilization. Here, we describe the rational redesign of a miniprotein, PPα, comprising a polyproline II helix, a loop, and an α helix. The redesign provides a de novo framework for in...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.9b00067
更新日期:2019-07-16 00:00:00
abstract::A topoisomer gel retardation assay has been used to examine the topological requirements for the formation of open promoter complexes on DNA minicircles carrying sigma 54-dependent promoters. In the absence of intercalators, individual topoisomers carrying both the nifL and nifF promoters could be resolved as discrete...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9701179
更新日期:1997-10-07 00:00:00
abstract::To probe the mechanism of chaperone substrate selection, we have investigated the kinetics of complex formation and dissociation between the molecular chaperone DnaK and a short peptide (Cro, representing amino acids 1-12 of the cro repressor protein). The Cro protein was N-terminally labeled with the environmentally ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00047a024
更新日期:1995-11-28 00:00:00
abstract::Naturally occurring interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural interruption ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.7b01010
更新日期:2018-02-20 00:00:00
abstract::The chicken and goose egg white lysozymes (ChEWL and GoEWL) are homologues, but differ in substrate specificity. ChEWL catalyzes the hydrolysis of the glycosidic bonds of bacterial peptidoglycans and chitin-derived substrates, while GoEWL is specific for bacterial peptidoglycans. The active-site aspartate 52 residue o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951671q
更新日期:1996-02-13 00:00:00
abstract::The ability to undergo large-scale domain rearrangements is essential for the substrate-binding function of periplasmic binding proteins (PBPs), which are indispensable for nutrient uptake in Gram-negative bacteria. Crystal structures indicate that PBPs typically adopt either an "open" unliganded configuration or a "c...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi902045p
更新日期:2010-03-09 00:00:00
abstract::Understanding the process of amyloidogenesis is important for the future treatment of misfolding-based diseases, such as Alzheimer's, spongiform encephalopathies, and other important disorders affecting humans. In this work, we have used one of the best-characterized models for folding and misfolding, the activation d...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900960s
更新日期:2009-11-10 00:00:00
abstract::Phospholipase A2 from Naja naja kaouthia venom was covalently coupled onto agarose beads using two different chemistries. The effect of micellar competitive inhibitors in the coupling media was evaluated. Enzyme bound to N-hydroxysuccinimide-activated agarose, which is reactive primarily toward epsilon-amino groups, h...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00083a007
更新日期:1993-08-17 00:00:00
abstract::Rat liver sinusoidal endothelial cells (LECs) mediate the removal of hyaluronan (HA) from the circulation via a specific Ca(2+)-independent endocytic receptor. To characterize the receptor biochemically, detergent-soluble extracts were prepared from crude LEC membranes. Using a dot blot assay to quantitate 125I-HA bin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00117a039
更新日期:1992-01-21 00:00:00
abstract::Silk fibroin exists in a number of different states, such as silk I and silk II, with different properties largely defined by differences in secondary structure composition. Numerous attempts have been made to control the transitions from silk I to silk II in vitro to produce high-performance materials. Of all the fac...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049344i
更新日期:2004-09-07 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) Vpu is an integral membrane protein that belongs to the viroporin family. Viroporins interact with cell membranes, triggering membrane permeabilization and promoting release of viral particles. In vitro electrophysiological methods have revealed changes in membrane ion curre...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi3011175
更新日期:2013-01-08 00:00:00
abstract::Fluoroaluminate and fluoroberyllate are potent inhibitors of the ATPase activity of myosin. Inhibition requires the presence of ADP, and much evidence has accumulated to suggest that the tetrahedral fluoroaluminate and fluoroberyllate ions act as phosphate analogues, binding with high affinity at the active site in th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00090a022
更新日期:1993-10-05 00:00:00
abstract::Ultraviolet resonance Raman (UV RR) spectra are reported for ferricytochrome c from tuna and horse heart at pH 1.6, 7, 10, and 13, representing distinct conformational states of the protein (states II, III, IV, and V, respectively). The spectra were obtained with pulsed laser excitation at 200 and 218 nm, via H2 Raman...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00339a035
更新日期:1985-08-27 00:00:00
abstract::Pectate lyase C (pelC) was the first protein in which the parallel beta-helix structure was recognized. The unique features of parallel beta-helix-containing proteins-a relatively simple topology and unusual interactions among side chains-make pelC an interesting protein to study with respect to protein folding. In th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi001900v
更新日期:2000-12-26 00:00:00
abstract::Bypass synthesis by DNA polymerase I was studied using synthetic 40-nucleotide-long gapped duplex DNAs each containing a site-specific abasic site analog, as a model system for mutagenesis associated with DNA lesions. Bypass synthesis proceeded in two general stages: a fast polymerization stage that terminated opposit...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9621324
更新日期:1997-02-18 00:00:00
abstract::Light-driven outward sodium-pumping rhodopsin (NaR) was recently found in marine bacteria. Krokinobacter eikastus rhodopsin 2 (KR2) actively transports sodium and lithium ions in NaCl and LiCl, respectively, while it pumps protons in KCl. NaR has a conserved NDQ (N112, D116, and Q123 in KR2) motif, and previous studie...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00741
更新日期:2016-10-18 00:00:00
abstract::The biosynthesis of the C ring of the antitumor antibiotic agent, tomaymycin, is proposed to proceed through five enzyme-catalyzed steps from l-tyrosine. The genes encoding these enzymes have recently been cloned and their functions tentatively assigned, but there is limited biochemical evidence supporting the assignm...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi200947w
更新日期:2011-09-06 00:00:00
abstract::The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00626a035
更新日期:1977-04-05 00:00:00
abstract::Ceruloplasmin is unique among the multicopper oxidases in that in addition to the usual copper stoichiometry of one Type 1 copper site and a Type 2/Type 3 trinuclear copper cluster, it contains two other Type 1 sites. This assignment of copper sites, based on copper quantitation, sequence alignment, and crystallograph...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980434v
更新日期:1998-06-30 00:00:00
abstract::All eight cysteine residues, C90, C94, C143, C147, C219, C325, C367, and C431, present in transmembrane domains of the Aspergillus nidulans NrtA nitrate transporter protein were altered individually by site-specific mutagenesis. The results indicate that six residues, C90, C147, C219, C325, C367, and C431, are not req...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047732e
更新日期:2005-04-12 00:00:00
abstract::Peptide inhibitors, specifically labeled at the alpha-amino terminus by dansylation, have been prepared by utilizing solid-phase peptide synthesis. Changes in fluorescence have been observed upon mixing these peptides with porcine pepsin that can be attributed to the formation of at least two complexes. Energy transfe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00528a023
更新日期:1981-12-08 00:00:00
abstract::The reaction of cytochrome c oxidase (COX) from Rhodobacter sphaeroides with hydrogen peroxide has been studied at alkaline (pH 8.5) and acidic (pH 6.5) conditions with the aid of a stopped-flow apparatus. Absorption changes in the entire 350-800 nm spectral range were monitored and analyzed by a global fitting proced...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi010115v
更新日期:2001-08-14 00:00:00
abstract::Proteins from the enhanced intracellular survival (Eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (AGs). Their upregulation confers drug resistance. Homologues of Eis are present in diverse bacteria, including many pathogens. Eis from Mycobacterium t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.5b00244
更新日期:2015-05-26 00:00:00
abstract::We have developed a simple method for reconstituting pure, integral membrane proteins into phospholipid-protein vesicles. The method does not depend on use of detergents or sonication. It has been used successfully with three different types of integral membrane proteins: UDPglucuronosyltransferase (EC 2.4.1.17) from ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00336a040
更新日期:1985-07-16 00:00:00
abstract::The periplasmic protein CusF, as a part of the CusCFBA efflux complex, plays a role in resistance to elevated levels of copper and silver in Escherichia coli. Although homologues have been identified in other Gram-negative bacteria, the substrate of CusF and its precise role in metal resistance have not been described...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0612622
更新日期:2006-09-19 00:00:00