- Mechanistic Insights into SARS-CoV-2 Main Protease Inhibition Reveals Hotspot Residues. [Journal Article]
- The main protease (Mpro) is a key enzyme responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication that causes the spread of the global pandemic novel coronavirus (nCOVID-19) infection. In the present study, multiple computational approaches such as docking, long-range molecular dynamics (MD) simulations, and binding free-energy (BFE) estimation techniques were empl…
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- Predictive Value of Serum Lipid for Intravenous Immunoglobulin Resistance and Coronary Artery Lesion in Kawasaki Disease. [Journal Article]
- CONCLUSIONS: Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-C and Apo A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.
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- Studies on the Interaction between Poly-Phosphane Gold(I) Complexes and Dihydrofolate Reductase: An Interplay with Nicotinamide Adenine Dinucleotide Cofactor. [Journal Article]
- A class of gold(I) phosphane complexes have been identified as inhibitors of dihydrofolate reductase (DHFR) from E. coli, an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), using NADPH as a coenzyme. In this work, to comprehend the nature of the interaction at the basis of these inhibitory effects, the binding properties of bis- and tris-phosphane gold(I) chl…
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- Phosphorylation compromises FAD binding and intracellular stability of wild-type and cancer-associated NQO1: Insights into flavo-proteome stability. [Journal Article]
- Over a quarter million of protein phosphorylation sites have been identified so far, although the effects of site-specific phosphorylation on protein function and stability, as well as their possible impact in the phenotypic manifestation in genetic diseases are vastly unknown. We investigated here the effects of phosphorylating S82 in human NADP(H):quinone oxidoreductase 1, a representative exam…
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- Severe riboflavin deficiency induces alterations in the hepatic proteome of starter Pekin ducks. [Journal Article]
- Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks wer…
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- Comparative evaluation of accuracy of periodontal probing depth and attachment levels using a Florida probe versus traditional probes. [Journal Article]
- CONCLUSIONS: Florida probe and CEJ probe have been shown to be more accurate and were found to be more consistent which were reproducible by two independent examiners.
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- Comparative evaluation of surgical modalities for coverage of gingival recession: An Armed Forces Medical College perspective. [Journal Article]
- CONCLUSIONS: Connective tissue grafts were statistically significantly superior to guided tissue regeneration for improvement in gingival recession reduction.
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- [Effect of periodontal therapy on metabolic control and serum biochemical markers in subjects with type 2 diabetes and chronic periodontitis]. [Journal Article]
- CONCLUSIONS: The initial periodontal therapy can significantly improve periodontal clinical parameters and HbA1c control, but the effect on venous fasting blood glucose was not revealed yet. In addition, initial periodontal therapy can also intervene serum phosphorus,calcium-phosphorus ratio, and the metabolism of lipid.
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- Thermodynamics of the GTP-GDP-operated conformational switch of selenocysteine-specific translation factor SelB. [Journal Article]
- SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNA(Sec)) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNA(Sec) to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangemen…
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- Entropy-driven binding of picomolar transition state analogue inhibitors to human 5'-methylthioadenosine phosphorylase. [Journal Article]
- Human 5'-methylthioadenosine phosphorylase (MTAP) links the polyamine biosynthetic and S-adenosyl-l-methionine salvage pathways and is a target for anticancer drugs. p-Cl-PhT-DADMe-ImmA is a 10 pM, slow-onset tight-binding transition state analogue inhibitor of the enzyme. Titration of homotrimeric MTAP with this inhibitor established equivalent binding and independent catalytic function of the t…
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- Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells. [Journal Article]
- Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor) o…
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- Antiatherogenic effect of isoflavones in ovariectomized apolipoprotein e-deficient mice. [Journal Article]
- The consumption of isoflavone-containing foods such as soybean and soybean products has been reported to have beneficial effects on the cardiovascular system in postmenopausal women. The present study was carried out to examine the mechanism underlying the beneficial effects of isoflavones in apolipoprotein (apo) E-deficient mice subjected to ovarian resection. Compared with sham-operated mice, o…
- Binding of a single zinc ion to one subunit of copper-zinc superoxide dismutase apoprotein substantially influences the structure and stability of the entire homodimeric protein. [Journal Article]
- The thermodynamics of zinc binding to metal-free (apo) human and bovine copper-zinc superoxide dismutases (SOD1) were measured using isothermal titration calorimetry. The apparent thermodynamics of zinc binding to the apoproteins were favorable (Ka > 108 M-1), with an observed stoichiometry of one zinc per homodimer. The change in heat capacity for the one-zinc binding event was large and negativ…
- Evaluation of riboflavin binding protein domain interaction using differential scanning calorimetry. [Journal Article]
- Riboflavin binding (or carrier) protein (RfBP) is a monomeric, two-domain protein, originally purified from hens' egg white. RfBP contains nine disulfide bridges; as a result, the protein forms a compact structure and undergoes reversible three-state thermal denaturation. This was demonstrated using a differential scanning calorimetry (DSC) method [Wasylewski M. (2000) J. Prot. Chem. 19(6), 523-5…
- The energetic cost of domain reorientation in maltose-binding protein as studied by NMR and fluorescence spectroscopy. [Journal Article]
- Maltose-binding protein (MBP) is a two-domain protein that undergoes a ligand-mediated conformational rearrangement from an "open" to a "closed" structure on binding to maltooligosaccharides. To characterize the energy landscape associated with this transition, we have generated five variants of MBP with mutations located in the hinge region of the molecule. Residual dipolar couplings, measured i…
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- Iron-sulfur cluster biosynthesis. A comparative kinetic analysis of native and Cys-substituted ISA-mediated [2Fe-2S]2+ cluster transfer to an apoferredoxin target. [Journal Article]
- ISA type proteins mediate cluster transfer to apoprotein targets. Rate constants have been determined for cluster transfer from Schizosaccharomyces pombe ISA to apo Fd. Substitution of the cysteine residues of ISA produced derivative proteins (C72A, C136A, and C138A) that were found to be at least as active in cluster transfer reactions as the native form at 25 degrees C (k(2) approximately 170 M…
- Relationship of early carotid artery disease with lipoprotein (a), apolipoprotein B, and fibrinogen in asymptomatic essential hypertensive patients and normotensive subjects. [Journal Article]
- CONCLUSIONS: The different correlates of IMT, CAL, and maximal degree of stenosis suggest that they reflect different events occurring in the arterial wall in response to aging, HT, and other risk factors, rather than simply different stages of the same atherosclerotic process.
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- Temperature dependence of dynamics and thermodynamics of the regulatory domain of human cardiac troponin C. [Journal Article]
- Binding of Ca(2+) to the regulatory domain of troponin C (TnC) in cardiac muscle initiates a series of protein conformational changes and modified protein-protein interactions that initiate contraction. Cardiac TnC contains two Ca(2+) binding sites, with one site being naturally defunct. Previously, binding of Ca(2+) to the functional site in the regulatory domain of TnC was shown to lead to a de…
- Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions. [Journal Article]
- CONCLUSIONS: The less distensible carotid wall in patients with KD compared with that in Cont without major alteration of the lipid profile is likely to be secondary to the changes in arterial walls after a diffuse vasculitis involving noncoronary arteries. These results indicate that the coronary arteries may be predisposed to accelerated atherosclerosis in patients with KD and CAL.
- Enhancement of the cAMP-induced apolipoprotein-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW 264 mouse macrophage cell line cells. [Journal Article]
- Apolipoprotein (apo) A-I generates high-density lipoprotein (HDL) by removing cellular cholesterol and phospholipid on the interaction with cells as a main source of plasma HDL. The reaction is induced by dibutylyl cyclic (dbc) adenosine monophosphate (AMP) in RAW 264, mouse macrophage cell line cells, and we investigated its pharmacologic modulation using this cell model. Release of cellular cho…
- Apolipoprotein E;-low density lipoprotein receptor interaction. Influences of basic residue and amphipathic alpha-helix organization in the ligand. [Journal Article]
- Conserved lysines and arginines within amino acids 140-150 of apolipoprotein (apo) E are crucial for the interaction between apoE and the low density lipoprotein receptor (LDLR). To explore the roles of amphipathic alpha-helix and basic residue organization in the binding process, we performed site-directed mutagenesis on the 22-kDa fragment of apoE (amino acids 1-191). Exchange of lysine and arg…
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- Counterpoint: to (measure apo) B or not to (measure apo) B: a critique of modern medical decision-making. [Journal Article]
- The measurement of apo B provides critical information that is complementary to that provided by the plasma and lipoprotein lipids for the assessment of coronary risk and the choice of appropriate pharmacological therapy. Why then is this measurement not in more widespread clinical use? I suggest two explanations. First, against the evidence, there is a lingering perception that problems persist …
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- Calorimetry of apolipoprotein-A1 binding to phosphatidylcholine-triolein-cholesterol emulsions. [Journal Article]
- The thermotropic properties of triolein-rich, low-cholesterol dipalmitoyl phosphatidylcholine (DPPC) emulsion particles with well-defined chemical compositions (approximately 88% triolein, 1% cholesterol, 11% diacyl phosphatidylcholine) and particle size distributions (mean diameter, approximately 1000-1100 A) were studied in the absence and presence of apolipoprotein-A1 by a combination of diffe…
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- Thermodynamics of heme-induced conformational changes in hemopexin: role of domain-domain interactions. [Journal Article]
- Hemopexin is a serum glycoprotein that binds heme with high affinity and delivers heme to the liver cells via receptor-mediated endocytosis. A hinge region connects the two non-disulfide-linked domains of hemopexin, a 35-kDa N-terminal domain (domain I) that binds heme, and a 25-kDa C-terminal domain (domain II). Although domain II does not bind heme, it assumes one structural state in apo-hemope…
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- Measurement of apolipoproteins B and A by radial immunodiffusion: methodological assessment and clinical applications. [Journal Article]Ann Biol Clin (Paris). 1994; 52(9):657-61.AB
- The clinical evaluation of apolipoproteins is of interest in order to characterize the risk profile for ischemic heart disease both in normolipidemic and hyperlipidemic subjects. In the non-specialized and/or small practice clinical laboratory, the measurement of some apolipoproteins can be undertaken by simple methods of immunological analysis, among which radial immunodiffusion can be of intere…
- Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice. [Journal Article]
- In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL-C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded …
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- Calorimetric determination of the energetics of the molten globule intermediate in protein folding: apo-alpha-lactalbumin. [Journal Article]
- High-sensitivity differential scanning calorimetry has been used to characterize the energetics of the molten globule state of apo-alpha-lactalbumin. This characterization has been possible by performing temperature scans at different guanidine hydrochloride (GuHCl) concentrations in order to experimentally define the temperature-GuHCl stability surface of the protein. Multidimensional analysis o…
- Effect of fish oil on atherosclerosis and lipoprotein metabolism. [Review]
- This review primarily covers work on the effects of dietary n-3 fatty acids on lipoprotein metabolism and atherosclerosis that has been done in a nonhuman primate model, the African green monkey, and puts it in context with work of others using humans and other experimental animals. Detection of effects of n-3 fatty acids in the monkey model was facilitated by a considerable enrichment of dietary…
- Postprandial effect of a high fat meal on plasma lipid, lipoprotein cholesterol and apolipoprotein measurements. [Journal Article]
- We investigated the effect of a fatty meal on plasma concentrations of lipids, apolipoproteins, and the cholesterol component of lipoproteins. Sixteen nonobese, healthy, asymptomatic males, 22-34 years of age, served as subjects for this study. None smoked, consumed more than two alcoholic drinks per day, or took any medication known to alter plasma lipids. After a 12 h fast, baseline plasma samp…