Proteome-wide probing of the dual NMT-dependent myristoylation tradeoff unveils potent, mechanism-based suicide inhibitors

N-myristoyltransferases (NMTs) catalyze protein myristoylation, a major and ubiquitous lipid modification. Originally thought to modify only N-terminal glycine alpha-amino groups (G-myristoylation), NMTs are now known to modify lysine epsilon-amino groups (K-myristoylation), the significance of which is uncertain. Here we exploited systematic structural proteomics analyses and a novel pipeline involving the Shigella IpaJ protease to discriminate K- and G-myristoylation with unprecedented accuracy and identify the specific features driving each modification. NMT-dependent K-myristoylation occurs post-translationally and only on lysines 1, 2, or 3 following G-myristoylation or caspase cleavage. Direct interactions between the substrate′s reactive amino group and the NMT catalytic base slow K-myristoylation catalysis. IpaJ unmasked novel K-myristoylation sites in a dozen human proteins. The unique properties of NMT-driven K-myristoylation allowed us to design potent, mechanism-based suicide NMT inhibitors. These analyses unravel the respective paths towards K-myristoylation, G-myristoylation, or NMT inhibition, which rely on a very subtle tradeoff embracing the chemical landscape around the reactive group.

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Investigation of the effect of ring size on the product distribution for the Schiff base reaction of 2-acetylcycloalkanones with diamino alkanes

Canadian Journal of Chemistry ◽

10.1139/v95-004 ◽

1995 ◽

Vol 73 (1) ◽

pp. 16-21 ◽

Cited By ~ 9

Author(s):

Raul G. Enriquez ◽

Juan M. Fernandez-G ◽

Ismael Leon ◽

William F. Reynolds ◽

Ji.-Ping Yang ◽

...

Keyword(s):

Schiff Base ◽

Condensation Reaction ◽

2D Nmr ◽

Product Distribution ◽

Major Product ◽

Ring Size ◽

Amino Group ◽

Amino Groups ◽

Removal of Organic Compounds with an Amino Group during the Nanofiltration Process

Membranes ◽

10.3390/membranes12010058 ◽

2021 ◽

Vol 12 (1) ◽

pp. 58

Author(s):

Renata Żyłła ◽

Magdalena Foszpańczyk ◽

Magdalena Olak-Kucharczyk ◽

Joanna Marszałek ◽

Stanisław Ledakowicz

Keyword(s):

Organic Compounds ◽

Natural Organic Matter ◽

Oxidation Product ◽

Membrane Filtration ◽

Separation Efficiency ◽

Ph Value ◽

Oxidation Products ◽

Low Molecular Weight ◽

Amino Group ◽

Amino Groups

The research covered the process of nanofiltration of low molecular weight organic compounds in aqueous solution. The article presents the results of experiments on membrane filtration of compounds containing amino groups in the aromatic ring and comparing them with the results for compounds without amino groups. The research was carried out for several commercial polymer membranes: HL, TS40, TS80, DL from various manufacturers. It has been shown that the presence of the amino group and its position in relation to the carboxyl group in the molecule affects the retention in the nanofiltration process. The research also included the oxidation products of selected pharmaceuticals. It has been shown that 4-Amino-3,5-dichlorophenol—a oxidation product of diclofenac and 4-ethylbenzaldehyde—a oxidation product of IBU, show poor separation efficiency on the selected commercial membranes, regardless of the pH value and the presence of natural organic matter (NOM). It has been shown that pre-ozonation of natural river water can improve the retention of pollutants removed.

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Anomalous phase behavior in blends of -SO3H terminated polystyrene with poly(n-butyl acrylate) containing a small amount of tertiary amino groups

e-Polymers ◽

10.1515/epoly.2008.8.1.917 ◽

2008 ◽

Vol 8 (1) ◽

Author(s):

Kenji Yamamoto ◽

Ayumi Nanakno ◽

Hiroyasu Masunaga ◽

Isamu Akiba

Keyword(s):

Butyl Acrylate ◽

Stoichiometric Composition ◽

Phase Region ◽

Molar Ratio ◽

Amino Group ◽

Amino Groups ◽

Two Phase ◽

Dimethylaminoethyl Methacrylate ◽

X Ray Scattering ◽

Tertiary Amino

Abstract Phase behavior in the blend of -SO3H terminated polystyrene (PSS) with poly(n-butyl acrylate-co-N,N-dimethylaminoethyl methacrylate) containing 6.0 mol% N,N-dimethylaminoethyl methacrylate (P1) is investigated by optical microscopy and small-angle X-ray scattering (SAXS). Comparing the miscibility of polystyrene/P1 blend, it is confirmed that the miscibility of the PSS/P1 blend is drastically improved by the hydrogen bonds between -SO3H and tertiary amino group. In addition, two-phase region of the PSS/P1 blend is split into two regions around the stoichiometric composition, in which the molar ratio of -SO3H to tertiary amino group is 1:1 stoichiometry. SAXS result shows that the PSS/P1 blend at stoichiometric composition forms a block copolymer-like aggregate and it takes a disorder state.

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pKa-Werte von Ethidiumbromid und 7-Amino-9-phenyl-10- äthyl-phenanthridinium-bromid / pKa-Values of Ethidiumbromide and 7-Amino-9-phenyl-10-ethyl-phenanthridinium- bromide

Zeitschrift für Naturforschung C ◽

10.1515/znc-1976-11-1205 ◽

1976 ◽

Vol 31 (11-12) ◽

pp. 656-660 ◽

Cited By ~ 12

Author(s):

Ingfried Zimmermann ◽

Herbert Zimmermann

Keyword(s):

Electronic Spectra ◽

Water Solution ◽

Ph Dependence ◽

Quantum Mechanical ◽

Amino Group ◽

Quantum Mechanical Calculations ◽

Acidic Water ◽

Amino Groups ◽

Electronic Density ◽

Decreasing Ph

Abstract Ethidiumbromide (1) has two amino groups in 2-and 7-position which are protonated in acidic water solution. Both pKa-values of 1 are determined at 20 °C by means of the pH-dependence of the electronic spectra using a iterative calculating procedure, pKa1 = 0.713, pKa2 = 2.43. Acetylation of 1 and quantum mechanical calculations lead to the conclusion that the electronic density at the 7-amino group is greater than in 2-position. Therefore with decreasing pH preferably the 7-amino group is protonated (pKa2). followed by the protonation of the 2-amino group (pKa1). The pKa of 7-amino-9-phenyl-10-ethyl-phenanthridinium-bromide in water solution at 20 °C is determined to pKa= 1 .2 5 .

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Effect of cross-linking agents on insulin associated responses in adipocytes

Canadian Journal of Biochemistry ◽

10.1139/o82-127 ◽

1982 ◽

Vol 60 (10) ◽

pp. 987-1000 ◽

Cited By ~ 2

Author(s):

H. Joseph Goren ◽

C. Ronald Kahn

Keyword(s):

Insulin Receptor ◽

Glucose Transport ◽

Free Amino ◽

Glucose Oxidation ◽

Insulin Binding ◽

Cross Linking ◽

Amino Group ◽

Amino Groups ◽

Disuccinimidyl Suberate ◽

Reactive Groups

The effect of 10 bifunctional cross-linking agents and four monofunctional analogues was studied on isolated adipocytes. [125I]Insulin binding and degradation, basal and insulin-stimulated glucose oxidation, and 3-O-methyl glucose uptake were measured. Two cross-linkers, which possess succinimide ester residues (disuccinimidyl suberate and dithiobis(succinimidyl propionate)) and react selectively with amino groups, appeared to react relatively specifically with the insulin receptor. Both produced a slight stimulation of basal glucose transport and metabolism, a marked inhibition of insulin-stimulated glucose transport and metabolism, and a marked decrease in insulin binding. Pretreatment of cells with unlabelled insulin partially blocked the effect of disuccinimidyl suberate, and as has been previously shown, disuccinimidyl suberate cross-linked insulin to its receptor. A monofunctional analogue of these compounds was 100-fold less active in altering cellular metabolic activity. Bisimidates, such as dimethyl suberimidate, dimethyl adipimidate, and dimethyl dithiobispropionimidate, also react with free amino groups but are more hydrophilic. These agents produced similar effects on glucose oxidation as the succinimide esters, but had little or no effect on insulin binding. The effects of these agents are not blocked by insulin and they do not cross-link insulin to its receptor. Mixed bifunctional reagents containing either a succinimide ester or an imidate and a group which reacts with thiols produced effects similar to the cross-linkers containing two succinimide groups or bisimidates, respectively. The bifunctional arylating agents difluorodinitrobenzene and bis(fluoronitrophenyl)sulfone produce marked effects on insulin binding and glucose oxidation at micromolar concentrations, but the monofunctional analogue fluorodinitrobenzene is almost equally active suggesting that with these compounds chemical modifications and not cross-linking was important. With neither the mixed bifunctional reagents, nor the arylating agents, did insulin pretreatment alter the effect of cross-linker and none of these agents cross-linked [125I]insulin to its receptor. These data suggest that the insulin receptor possesses a free amino group in a hydrophobic environment in its active site. A reactive amino group in a hydrophilic environment as well as other reactive groups are also present in some component of the insulin receptor–effector complex. Chemical modification or cross-linking of these functional groups results in an inhibition or mimicking of insulin action. Further study will be required to identify the exact locus of these sites.

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Isoelectric points of erabutoxins and monoacyl derivatives of erabutoxin b. Estimation of the pK values of amino groups in erabutoxins by using isoelectric-focusing data

Biochemical Journal ◽

10.1042/bj2030427 ◽

1982 ◽

Vol 203 (2) ◽

pp. 427-433 ◽

Cited By ~ 2

Author(s):

N UI ◽

C Takasaki ◽

N Tamiya

Keyword(s):

Isoelectric Focusing ◽

Isoelectric Point ◽

Amino Group ◽

Amino Groups ◽

Sea Snake ◽

Isoelectric Points ◽

Point Data ◽

Laticauda Semifasciata ◽

Erabutoxin B ◽

Derivatives Of

The isoelectric points of erabutoxins a, b and c, neurotoxic proteins of a sea snake, Laticauda semifasciata, were determined by density-gradient isoelectric focusing. The same measurement was also made with monoacyl derivatives of erabutoxin b, in which each one of all amino groups had been either acetylated or propionylated. Erabutoxins a and b showed the same isoelectric point at pH 9.68. The values for [1-N alpha-acetyl-arginine]-, [15-N6-acetyl-lysine]-, [27-N6-acetyl-lysine]-, [47-N6-propionyl-lysine]- and [51-N6-acetyl-lysine]-erabutoxin b were at pH 9.52, 9.31, 9.45, 9.22 and 9.09 respectively, being definitely different from each other and lower than the value for the unmodified molecule. The isoelectric point of erabutoxin c, which is [51-asparagine]-erabutoxin b, was the same as that of [51-N6-acetyl-lysine]erabutoxin b. Assuming that no change in pK occurs on monoacylation, the pK values of amino groups in erabutoxin b were calculated from the isoelectric-point data. It is indicated that the pK values of zeta-amino groups differ markedly from each other and that the value of alpha-amino group is anomalously high.

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The configuration of 2,6-diamino-3-hydroxypimelic acid in microbial cell walls

Biochemical Journal ◽

10.1042/bj1150797 ◽

1969 ◽

Vol 115 (4) ◽

pp. 797-805 ◽

Cited By ~ 9

Author(s):

H R Perkins

Keyword(s):

Cell Wall ◽

Hydroxy Group ◽

Cell Walls ◽

Optical Rotation ◽

Periodate Oxidation ◽

Ring Closure ◽

Diaminopimelic Acid ◽

Amino Group ◽

Amino Groups ◽

Peptide Linkage

β-Hydroxydiaminopimelic acid, together with some diaminopimelic acid, occurs in the cell-wall mucopeptide of certain Actinomycetales. These components were converted into their di-DNP derivatives and separated by chromatography. Hence the relative proportions present in the cell walls of a number of species were measured. The problem of acid-induced inversion of configuration was studied. Of the diaminohydroxypimelic acids isomer B (see Scheme 2; amino groups meso, hydroxy group threo to its neighbouring amino group) always predominated but a small proportion of isomer D (amino groups l, hydroxy group erythro) also occurred. The configuration of the diaminohydroxypimelic acids was determined by periodate oxidation to glutamic γ-semialdehyde, which underwent spontaneous ring-closure. Reduction with sodium borohydride produced optically active proline, the configuration of which was determined by direct measurement of the optical rotation of DNP-proline. Un-cross-linked diaminohydroxypimelic acid in the cell wall was oxidized with periodate in the presence of ammonia. Since the remaining amino group was bound in peptide linkage, ring-closure was prevented and borohydride reduction of the aldehyde–ammonia presumed to be present resulted in the formation of ornithine. The quantity of ornithine was used as a measure of the degree of cross-linking.

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Application of Hyperbranched Polymer with Terminal Amino in Dyeing Process of Microfiber Synthetic Leather

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.393-395.1114 ◽

2011 ◽

Vol 393-395 ◽

pp. 1114-1118

Author(s):

Long Fang Ren ◽

Guo Hui Zhao ◽

Tao Tao Qiang ◽

Jing Xian Wang ◽

Xue Chuan Wang

Keyword(s):

Uptake Rate ◽

Hyperbranched Polymer ◽

Succinic Anhydride ◽

Amino Group ◽

Dye Uptake ◽

Amino Groups ◽

Synthetic Leather ◽

Dyeing Process ◽

Terminal Amino ◽

Polymerization Method

Hyperbranched polymer with different contents of terminal amino group synthesized with succinic anhydride and DETA through the molten polymerization method was used in the dying process of microfiber synthetic leather substrate as color fixing agent. The effect on dye-uptake, surface chromas of microfiber synthetic leather substrate, wet and dry rub fastness was discussed. The result indicated that when the dosage of hyperbranched polymer with 5.85% terminal amino groups was 0.8%, the dye uptake rate was 92.92% and surface chroma was the best, the wet and dry rub fastness of microfiber synthetic leather substrate were almost unchanged.

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(E)-N,N-Diethyl-2,6-diisopropyl-4-[2-(4-nitrophenyl)ethenyl]aniline

Acta Crystallographica Section E Structure Reports Online ◽

10.1107/s1600536813030948 ◽

2013 ◽

Vol 69 (12) ◽

pp. o1785-o1786

Author(s):

Christoph Wink ◽

Dieter Schollmeyer ◽

Heiner Detert

Keyword(s):

Steric Hindrance ◽

Dihedral Angles ◽

Amino Group ◽

Asymmetric Unit ◽

Amino Groups ◽

Structural Support ◽

Pyramidal Geometry ◽

Compound C ◽

Phenylene Group ◽

Independent Molecules

The title compound, C24H32N2O2, was prepared by Horner olefination of 4-diethylamino-3,5-diisopropylbenzaldehyde and diethylp-nitrobenzylphosphonate. There are two independent molecules (AandB) in the asymmetric unit. Their main axes, defined by the line connecting the N atoms of the nitro and amino groups, open an angle of 79.42 (3)°. Steric hindrance around the amino group is reflected in a long aryl C—N bond [1.434 (3) Å for moleculeAand 1.440 (3) Å for moleculeB], a pyramidal geometry [angle sum = 350.0 (2)° for moleculeAand 349.6 (2)° for moleculeB], and dihedral angles between the phenylene group and the plane defined by the CH2—N—CH2unit of 86.9 (3)° for moleculeAand 88.3 (3)° for moleculeB. This gives structural support for the electronic decoupling of the amino group from the nearly planar nitrostilbene moiety (r.m.s. deviation for C, N and O atoms = 0.097 for moleculeAand 0.107 Å for moleculeB).

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Inhibition Of Cholesterol Atherosclerosis In Rabbits By Amino Imino Propene Diacetate

10.1055/s-0038-1652721 ◽

1981 ◽

Author(s):

B I Weigensberg ◽

S Katz ◽

J Lough ◽

R H More

Keyword(s):

Tissue Culture ◽

Surface Area ◽

Atherosclerotic Plaques ◽

Amino Group ◽

Amino Groups ◽

Ldl Uptake ◽

Arterial Smooth Muscle Cells ◽

Preliminary Study

Previous studies have shown that in vitro blockage of the ε amino group of lysine in LDL by acetoacetylation enhances LDL uptake by macrophages and liver cells and inhibits uptake of LDL by fibroblasts in tissue culture. Amino imino propene diacetate (AIPD) is a compound which is absorbed into the blood after feeding and which blocks the ε amino group of lysine in LDL for short periods of time after which the AIPD dissociates from LDL and is excreted in the urine. AIPD does not inhibit absorption of either 14C labelled or unlabelled cholesterol from the gastrointestinal tract. In a preliminary study it was found that 19 rabbits fed 300 mg crude AIPD along with 500 mg cholesterol per day in their food for 14 weeks showed 13.0 ± 3.3 (mean ± S.E.) % of their total aortic intimal surface area covered with grossly visible atherosclerotic plaques. In comparison 13 control rabbits fed 500 mg cholesterol per day in their food for 14 weeks showed 33.9 ± 6.0% of their total aortic intimal surface area covered with atherosclerotic plaques. (P< 0.01) These in vivo observations suggest that the inhibition of atherosclerosis by AIPD might be related to a reduction in the number of free lysine amino groups in LDL. In previous studies, we reported that dietary induced lysine deficiency could inhibit atherosclerosis. These and other studies suggest that blocking or reducing the number of free lysine ε, amino groups in LDL appears to enhance LDL uptake and clearance by liver and macrophage type cells and reduces LDL uptake by arterial smooth muscle cells and fibroblasts in vivo. The combination of these effects appears to offer some protection against the development of cholesterol atherosclerosis.

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