Chemical Inhibitors of Epigenetic Methyllysine Reader Proteins.

Abstract:

:Protein methylation is a common post-translational modification with diverse biological functions. Methyllysine reader proteins are increasingly a focus of epigenetics research and play important roles in regulating many cellular processes. These reader proteins are vital players in development, cell cycle regulation, stress responses, oncogenesis, and other disease pathways. The recent emergence of a small number of chemical inhibitors for methyllysine reader proteins supports the viability of these proteins as targets for drug development. This article introduces the biochemistry and biology of methyllysine reader proteins, provides an overview of functions for those families of readers that have been targeted to date (MBT, PHD, tudor, and chromodomains), and reviews the development of synthetic agents that directly block their methyllysine reading functions.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Milosevich N,Hof F

doi

10.1021/acs.biochem.5b01073

subject

Has Abstract

pub_date

2016-03-22 00:00:00

pages

1570-83

issue

11

eissn

0006-2960

issn

1520-4995

journal_volume

55

pub_type

杂志文章,评审
  • Thermal behavior of synthetic sphingomyelin-cholesterol dispersions.

    abstract::The thermotropic behavior of aqueous dispersions of palmitoylsphingomyelin-cholesterol and lignoceryl-sphingomyelin-cholesterol mixtures has been examined by high-sensitivity differential scanning calorimetry. When less than 25 mol % cholesterol is mixed with either sphingomyelin, the calorimetric endotherm is compose...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00577a042

    authors: Estep TN,Mountcastle DB,Barenholz Y,Biltonen RL,Thompson TE

    更新日期:1979-05-15 00:00:00

  • Comparisons of redox kinetics of methemerythrin and mu-sulfidomethemerythrin. Implications for interactions with cytochrome b5.

    abstract::We have examined the effects on redox kinetics of changing the reduction potential of the mu-oxo-bridged binuclear iron center in octameric hemerythrin (Hr) from Phascolopsis gouldii. The opportunity to examine such effects is provided by the availability of mu-sulfidomethemerythrin (mu-S2-metHr), whose [Fe(III),Fe(II...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00400a033

    authors: Pearce LL,Utecht RE,Kurtz DM Jr

    更新日期:1987-12-29 00:00:00

  • Proteolytic activation of protein C from bovine plasma.

    abstract::Protein C is a vitamin K dependent protein present in bovine plasma (Stenflo, J. (1976), J. Biol. Chem. 251, 355). It is a glycoprotein (mol wt approximately 62 000) composed of a heavy chain (mol wt 41 000) and a light chain (mol wt 21 000). The heavy chain has an amino-terminal sequence of Asp-Thr-Asn-Gln and contai...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00667a022

    authors: Kisiel W,Ericsson LH,Davie EW

    更新日期:1976-11-02 00:00:00

  • Lipid-free structure and stability of apolipoprotein A-I: probing the central region by mutation.

    abstract::To probe the structure and stability of the central region of lipid-free apolipoprotein (apo) A-I (residues 123-165), we studied the effects of four mutations made in this region on the conformation, stability, dimyristoylphosphatidylcholine (DMPC) binding kinetics, and size of discoidal reconstituted high-density lip...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi025807d

    authors: Gorshkova IN,Liu T,Zannis VI,Atkinson D

    更新日期:2002-08-20 00:00:00

  • Purification and properties of squirrel monkey (Saimiri sciureus) corticosteroid binding globulin.

    abstract::Corticosteroid binding globulin (CBG), a serum glycoprotein which binds glucocorticoids and progestins with high affinity, is widely distributed throughout the animal world. Although its charge and size characteristics have largely been conserved across species, we found the behavior of CBG in squirrel monkey (Saimiri...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00407a046

    authors: Kuhn RW,VestWeber C,Siiteri PK

    更新日期:1988-04-05 00:00:00

  • Importance of loops of mitochondrial ADP/ATP carrier for its transport activity deduced from reactivities of its cysteine residues with the sulfhydryl reagent eosin-5-maleimide.

    abstract::The effects of various compounds such as the transport substrate ADP and the transport inhibitors carboxyatractyloside (CATR) and bongkrekic acid (BKA) on the labeling of cysteine residues in the ADP/ATP carrier of bovine heart submitochondrial particles by the SH reagent eosin-5-maleimide (EMA) were studied. Of the f...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00198a019

    authors: Majima E,Shinohara Y,Yamaguchi N,Hong YM,Terada H

    更新日期:1994-08-16 00:00:00

  • Pseudohyperphosphorylation causing AD-like changes in tau has significant effects on its polymerization.

    abstract::The microtubule-associated protein tau, in a hyperphosphorylated form, aggregates into insoluble paired-helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. In AD, there is approximately 8 mol of phosphate per mole of tau distributed among approximately 30 PHF phosphorylation sites as compared t...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi900602h

    authors: Sun Q,Gamblin TC

    更新日期:2009-06-30 00:00:00

  • Thermodynamics of bovine spleen galectin-1 binding to disaccharides: correlation with structure and its effect on oligomerization at the denaturation temperature.

    abstract::Isothermal titration calorimetry (ITC) measurements of the binding 1-beta carbohydrate-substituted galactopyranoside derivatives to galectin-1 from bovine spleen, a dimer with one binding site per subunit, were performed at 283-285 and 298 K. The disaccharides were lactose, methyl beta-lactoside, lactulose, 4-O-beta-D...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9716478

    authors: Schwarz FP,Ahmed H,Bianchet MA,Amzel LM,Vasta GR

    更新日期:1998-04-28 00:00:00

  • Optical spectroscopy of nicotinoprotein alcohol dehydrogenase from Amycolatopsis methanolica: a comparison with horse liver alcohol dehydrogenase and UDP-galactose epimerase.

    abstract::The NADH absorbance spectrum of nicotinoprotein (NADH-containing) alcohol dehydrogenase from Amycolatopsis methanolica has a maximum at 326 nm. Reduced enzyme-bound pyridine dinucleotide could be reversibly oxidized by acetaldehyde. The fluorescence excitation spectrum for NADH bound to the enzyme has a maximum at 325...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi972115u

    authors: Piersma SR,Visser AJ,de Vries S,Duine JA

    更新日期:1998-03-03 00:00:00

  • Copurification of the FpvA ferric pyoverdin receptor of Pseudomonas aeruginosa with its iron-free ligand: implications for siderophore-mediated iron transport.

    abstract::The Pseudomonas aeruginosa FpvA receptor is a TonB-dependent outer membrane transport protein that catalyzes uptake of ferric pyoverdin across the outer membrane. Surprisingly, FpvA expressed in P. aeruginosa grown in an iron-deficient medium copurifies with a ligand X that we have characterized by UV, fluorescence, a...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi990421x

    authors: Schalk IJ,Kyslik P,Prome D,van Dorsselaer A,Poole K,Abdallah MA,Pattus F

    更新日期:1999-07-20 00:00:00

  • Solution structure of the (+)-cis-anti-benzo[a]pyrene-dA ([BP]dA) adduct opposite dT in a DNA duplex.

    abstract::Minor adducts, derived from the covalent binding of anti-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide to cellular DNA, may play an important role in generating mutations and initiating cancer. We have applied a combined NMR-computational approach including intensity based refinement to determine the solution structure of...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi991212f

    authors: Mao B,Gu Z,Gorin A,Chen J,Hingerty BE,Amin S,Broyde S,Geacintov NE,Patel DJ

    更新日期:1999-08-17 00:00:00

  • Location of the maltosyl isothiocyanate binding site on the human erythrocyte glucose transporter.

    abstract::The covalent affinity probe maltosyl isothiocyanate (MITC) has been used previously to identify the glucose transporter of human erythrocytes as a component of band 3. By use of limited proteolysis, the site on the Mr 100 000 protein to which MITC attaches has been localized to a 17 000-dalton region near the center o...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00331a001

    authors: Shelton RL Jr,Langdon RG

    更新日期:1985-05-07 00:00:00

  • Inactivation of C30A trimethylamine dehydrogenase by N-cyclopropyl-alpha-methylbenzylamine, 1-phenylcyclopropylamine, and phenylhydrazine.

    abstract::Trimethylamine dehydrogenase (TMADH) from the bacterium Methylophilus methylotrophus (sp. W(3)A(1)) and its C30A mutant were inactivated with three known inactivators of monoamine oxidase, namely, phenylhydrazine, N-cyclopropyl-alpha-methylbenzylamine, and 1-phenylcyclopropylamine. All three compounds irreversibly ina...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi0105126

    authors: Mitchell DJ,Nikolic D,Jang MH,van Breemen RB,Hille R,Silverman RB

    更新日期:2001-07-24 00:00:00

  • Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases.

    abstract::Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi011389l

    authors: Iversen LF,Andersen HS,Møller KB,Olsen OH,Peters GH,Branner S,Mortensen SB,Hansen TK,Lau J,Ge Y,Holsworth DD,Newman MJ,Hundahl Møller NP

    更新日期:2001-12-11 00:00:00

  • Determination of Fe-CO geometry in the subunits of carbonmonoxy hemoglobin M Boston using femtosecond infrared spectroscopy.

    abstract::We have undertaken ultrafast infrared (IR) spectroscopic studies in order to elucidate the geometry of bound CO in the alpha and beta subunits of hemoglobin (Hb) M Boston 13CO. Hb M Boston is a mutant human Hb in which the distal histidine in the alpha subunits is replaced by a tyrosine. The IR absorptions of bound 13...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00073a013

    authors: Lian T,Locke B,Kitagawa T,Nagai M,Hochstrasser RM

    更新日期:1993-06-08 00:00:00

  • Two-dimensional 1H NMR studies of cytochrome c: hydrogen exchange in the N-terminal helix.

    abstract::The hydrogen exchange behavior of the N-terminal helical segment in horse heart cytochrome c was studied in both the reduced and the oxidized forms by use of two-dimensional nuclear magnetic resonance methods. The amide protons of the first six residues are not H bonded and exchange rapidly with solvent protons. The m...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00353a025

    authors: Wand AJ,Roder H,Englander SW

    更新日期:1986-03-11 00:00:00

  • Purification and characterization of two unique forms of cytochrome P-450 from rabbit nasal microsomes.

    abstract::Two forms of cytochrome P-450, designated P-450NMa and P-450NMb, were purified to electrophoretic homogeneity from rabbit nasal microsomes. The purified cytochromes, which contained 14-16 nmol of P-450/mg of protein, exhibited apparent monomeric molecular weights of 49,500 and 51,000, respectively. As indicated by sev...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00422a007

    authors: Ding XX,Coon MJ

    更新日期:1988-11-01 00:00:00

  • Selective targeting of G-quadruplex using furan-based cyclic homooligopeptides: effect on c-MYC expression.

    abstract::Quadruplex-specific molecules can serve as suitable drugs in cancer therapy. We have synthesized a pair of furan-based cyclic homooligopeptides, ligand 1 and ligand 2, to specifically target G-quadruplexes. We have shown by CD spectroscopy and UV melting that these ligands can effectively induce G-quadruplex structure...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi1005927

    authors: Agarwal T,Roy S,Chakraborty TK,Maiti S

    更新日期:2010-09-28 00:00:00

  • Heparin enhances the inhibition of factor Xa by protein C inhibitor in the presence but not in the absence of Ca2+.

    abstract::Protein C inhibitor (PCI) is a versatile serine protease inhibitor with both pro- and anticoagulant and other properties. Interactions of certain ligands with PCI, including heparin, affect its specificity for proteases. In this study, heparin was found to enhance PCI inhibition of factor Xa up to 42-fold in the prese...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi802138m

    authors: Sun W,Eriksson AS,Schedin-Weiss S

    更新日期:2009-02-10 00:00:00

  • Effects of lipids and long-chain alkyl derivatives on the activity of (Ca2+-Mg2+)-ATPase.

    abstract::The ATPase activity of the (Ca2+-Mg2+)-ATPase reconstituted into bilayers of phosphatidylcholines depends on the fatty acyl chain length of the phospholipids. It is shown that the fluorescence response to Ca2+ of the ATPase modified with fluorescein isothiocyanate is also dependent on phospholipid structure and is int...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00371a043

    authors: Froud RJ,East JM,Jones OT,Lee AG

    更新日期:1986-11-18 00:00:00

  • Status of empirical methods for the prediction of protein backbone topography.

    abstract::An empirical preduction algorithm which uses information on the shrs on either side) interactions in 20 proteins to assign every residue in a protein to one of five conformational states is described. The conformational states are defined in terms of the backbone dihedral angles of the residue so that the prediction a...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00668a030

    authors: Maxfield FR,Scheraga HA

    更新日期:1976-11-16 00:00:00

  • Specific heterodimer formation by the cytoplasmic domains of the b and b' subunits of cyanobacterial ATP synthase.

    abstract::The soluble domains of the b and b' subunits of the ATP synthase of the cyanobacterium Synechocystis PCC 6803 were expressed with His tags attached to their N-termini. Following purification, the polypeptides were characterized by chemical cross-linking, analytical ultracentrifugation, and circular dichroism spectrosc...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi001821j

    authors: Dunn SD,Kellner E,Lill H

    更新日期:2001-01-09 00:00:00

  • Penicillanic acid sulfone: an unexpected isotope effect in the interaction of 6 alpha- and 6 beta-monodeuterio and of 6,6-dideuterio derivatives with RTEM beta-lactamase from Escherichia coli.

    abstract::Penicillanic acid sulfone (1) is both a substrate and an inactivator of the RTEM beta-lactamase. About 7000 hydrolytic events occur before enzyme inactivation. The 6,6-dideuterio sulfone shows a 3-fold acceleration of both the hydrolysis reaction and the enzyme inactivation. The kinetic and spectroscopic results are n...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00516a003

    authors: Brenner DG,Knowles JR

    更新日期:1981-06-23 00:00:00

  • The amino acid sequence of chick skin collagen alpha1-CB7.

    abstract::The amino acid sequence of chick skin collagen alpha1-CB7, the 268 CNBr peptide from the helical portion of the alpha1 chain, has been determined by automatic and manual degradation of tryptic and chymotryptic peptides, and of the COOH-terminal fragment produced by cleavage with animal collagenase. The resulting seque...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00684a013

    authors: Highberger JH,Corbett C,Kang AH,Gross J

    更新日期:1975-07-01 00:00:00

  • Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools.

    abstract::8-OxoGua (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. MutT protein of Escherichia coli specifically degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to correspondi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi047550k

    authors: Ito R,Hayakawa H,Sekiguchi M,Ishibashi T

    更新日期:2005-05-03 00:00:00

  • Molecular basis for the inhibition of HMGA1 proteins by distamycin A.

    abstract::The molecular mechanism for the displacement of HMGA1 proteins from DNA is integral to disrupting their cellular function, which is linked to many metastatic cancers. Chemical shift and NOESY NMR experiments provide structural evidence for the displacement of an AT hook peptide (DNA binding motif of HMGA1 proteins) by...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi200822c

    authors: Smith AE,Buchmueller KL

    更新日期:2011-09-27 00:00:00

  • The crystal structure of the Escherichia coli maltodextrin phosphorylase-acarbose complex.

    abstract::Acarbose is a naturally occurring pseudo-tetrasaccharide. It has been used in conjunction with other drugs in the treatment of diabetes where it acts as an inhibitor of intestinal glucosidases. To probe the interactions of acarbose with other carbohydrate recognition enzymes, the crystal structure of E. coli maltodext...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi9828573

    authors: O'Reilly M,Watson KA,Johnson LN

    更新日期:1999-04-27 00:00:00

  • 2.3 A resolution X-ray crystal structure of the bisubstrate analogue inhibitor salicylhydroxamic acid bound to human myeloperoxidase: a model for a prereaction complex with hydrogen peroxide.

    abstract::The X-ray crystal structure of a salicylhydroxamic acid (SHA) inhibitory complex with human myeloperoxidase (MPO) has been determined at 2.3 A resolution. The aromatic ring of the inhibitor binds to a hydrophobic region at the entrance to the distal heme pocket between heme pyrrole ring D and the side chain of Arg 239...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi960577m

    authors: Davey CA,Fenna RE

    更新日期:1996-08-20 00:00:00

  • Product Release Mechanism Associated with Structural Changes in Monomeric l-Threonine 3-Dehydrogenase.

    abstract::A short chain dehydrogenase like l-threonine 3-dehydrogenase (SDR-TDH) from metagenome data (mtTDH) was identified by database mining. Its enzymatic properties suggested that mtTDH has unique characteristics relative to other SDR-TDHs, including two mesophilic and thermophilic SDR-TDHs identified in this study. The ac...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.7b00832

    authors: Motoyama T,Nakano S,Yamamoto Y,Tokiwa H,Asano Y,Ito S

    更新日期:2017-10-31 00:00:00

  • Thermodynamic characterization of naturally occurring RNA single mismatches with G-U nearest neighbors.

    abstract::Due to their prevalence and roles in biological systems, single mismatches adjacent to G-U pairs are important RNA structural elements. Since there are only limited experimental values for the stability of single mismatches adjacent to G-U pairs, current algorithms using free energy minimization to predict RNA seconda...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi800471z

    authors: Davis AR,Znosko BM

    更新日期:2008-09-23 00:00:00