Mlab — A mathematical modeling tool

Knott, Gary D.

doi:10.1016/0010-468x(79)90075-8

Cited by 383 publications

(134 citation statements)

References 6 publications

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“…These values were verified using nonlinear least-squares fitting of the data to the MichaelisMenten equation (Knott, 1979). Inasmuch as our data (Siebens and Kregenow, 1980;Kregenow et al, 1985) and those of Cala (1980) strongly suggest that Na enters in exchange for H+ (or is cotransported with OH-), special care was taken to keep pH constant .…”

Section: Calculationsmentioning

confidence: 55%

Volume-regulatory responses of Amphiuma red cells in anisotonic media. The effect of amiloride.

Siebens¹,

Kregenow²

1985

The Journal of General Physiology

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Amphiuma red cells were incubated for several hours in hypotonic or hypertonic media. They regulate their volume in both media by using ouabain-insensitive salt transport mechanisms . After initially enlarging osmotically, cells in hypotonic media return toward their original size by losing K, Cl, and H2O. During this volume-regulatory decrease (VRD) response, K loss results from a >10-fold increase in K efflux . Cells in hypertonic media initially shrink osmotically, but then return toward their original volume by gaining Na, Cl, and H2O. The volume-regulatory increase (VRI) response involves a large (>100-fold) increase in Na uptake that is entirely blocked by the diuretic amiloride (10-g M). Na transport in the VRI response shares many of the characteristics of amiloride-sensitive transport in epithelia: (a) amiloride inhibition is reversible ; (b) removal of amiloride from cells pretreated with amiloride enhances Na uptake relative to untreated controls ; (c) amiloride appears to act as a competitive inhibitor (K i = 1-3 AM) of Na uptake; (d) Na uptake is a saturable function of external Na (K m -29 mM); (e) Li can substitute for Na but K cannot . Anomalous Na/K pump behavior is observed in both the VRD and the VRI responses. In the VRD response, pump activity increases 3-fold despite a decrease in intracellular Na concentration, while in the VRI response, a 10-fold increase in pump activity is observed when only a doubling is predicted from increases in intracellular Na .

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Section: Calculationsmentioning

confidence: 55%

Volume-regulatory responses of Amphiuma red cells in anisotonic media. The effect of amiloride.

Siebens¹,

Kregenow²

1985

The Journal of General Physiology

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“…The data were analyzed by mathematical modeling using MLAB (27). All of the measured data fit well to a trimeric model, and a representative result obtained for 1.8 M BsIFTase is presented.…”

Section: Methodsmentioning

confidence: 89%

Structural and Functional Insights into Intramolecular Fructosyl Transfer by Inulin Fructotransferase

Jung

Hong²,

Lee

et al. 2007

Journal of Biological Chemistry

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Inulin fructotransferase (IFTase), a member of glycoside hydrolase family 91, catalyzes depolymerization of ␤-2,1-fructans inulin by successively removing the terminal difructosaccharide units as cyclic anhydrides via intramolecular fructosyl transfer. The crystal structures of IFTase and its substratebound complex reveal that IFTase is a trimeric enzyme, and each monomer folds into a right-handed parallel ␤-helix. Despite variation in the number and conformation of its ␤-strands, the IFTase ␤-helix has a structure that is largely reminiscent of other ␤-helix structures but is unprecedented in that trimerization is a prerequisite for catalytic activity, and the active site is located at the monomer-monomer interface. Results from crystallographic studies and site-directed mutagenesis provide a structural basis for the exolytic-type activity of IFTase and a functional resemblance to inverting-type glycosyltransferases.Fructans are polysaccharides composed of linear and branched polymers of fructose linked to sucrose through glycosidic bonds of various linkage types. They have been conceived as one of the principal stored forms of energy in 15% of higher plants, as well as in a wide range of bacteria and fungi (1). Several plant fructosyltransferases, each with a distinct substrate and glycosidic bond linkage-type specificity, have been suggested to be involved in the sequential enzymatic steps that produce fructans such as ␤-2,6-linked levan and ␤-2,1-linked inulin. In this process, fructose is first linked to vacuolar sucrose, and then fructosyl units are successively added to the resulting trisaccharide (1, 2). Not only do plant fructans play a major role as storage carbohydrates, but they are also implicated in additional physiological functions in plants, such as drought and cold tolerance (1). By contrast, in bacteria, the multifunctional enzymes levansucrase (3) and inulosucrase (4) catalyze fructan biosynthesis, producing inulin and levan, the predominant bacterial fructans, respectively. Details of the levan biosynthetic mechanism in bacteria were recently revealed by structural studies of levansucrase (3, 5).Fructan-degrading enzymes that function primarily in the mobilization of stored fructans in plants and microbes have also been characterized. Just recently, the plant fructan hydrolases (EC 3.2.1) were found to catalyze the hydrolysis of levan and inulin via an exclusively exolytic mechanism that releases successive terminal fructose units (6). The presence of these fructan exohydrolases, even in non-fructan-containing plants, suggests an additional, defensive role for these enzymes against pathogenic bacteria (2).In bacteria, two distinctly different classes of enzymes perform fructan degradation. One of these classes includes two hydrolases, levanase (EC 3.2.1.65) and inulinase (EC 3.2.1.7), which exhibit both endo-and exotype hydrolytic activities. Classifications based on sequence similarity (7) (CAZy; www. cazy.org/CAZY/index.html) place these plant and microbial hydrolytic enzymes into the GH32...

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“…Samples were incubated for 1 h prior to analysis, and no change in signal was observed when the samples were incubated for an additional 12 h. Data points represent a time average of 3 min. The data were fit applying a specialized algorithm (Fairman et al, 1995) encoded in MLAB (Civilised Software) (Knott, 1979).…”

Section: Circular Dichroismmentioning

confidence: 99%

Structural characterization of the tumor suppressor p16, an ankyrin‐like repeat protein

Boice¹,

Fairman²

1996

Protein Science

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The p16 protein has been identified as a tumor suppressor that functions by inhibiting the cyclin-dependent kinases CDK4 and CDK6. Deletions or point mutations in the p16 gene have been found in a number of human cancers, emphasizing its importance in regulating cell cycle progression. Inhibition by p16 occurs through protein-protein interactions with its targets. This is not surprising, since p16 is thought to contain ankyrin-like repeats, motifs implicated in protein-protein interactions. Our goal was to identify structural characteristics of p16 not only as an important step towards understanding CDK4 inhibition but also to explore the role of ankyrin repeats in the p16 structure, as no detailed structure of any protein containing these motifs has been reported. We have expressed, refolded, and purified p16 from E. coli and have shown it to be functionally active by specific binding to CDK4. Analytical ultracentrifugation has shown that p16 weakly self-associates to form dimers with a Kd = 270 pM. The CD spectrum indicates that the protein is composed of 33% a-helix, 22% P-sheet, 19% p-turn, and 27% other (which includes aromatic and random coil contributions). Further CD experiments suggest that p16 exhibits low structural stability with a AG of -2.3 kcal/mol. This weak stability is a consequence of a highly dynamic structure as measured by ANS-binding, NMR hydrogendeuterium exchange, and fluorescence. It is possible that a well-defined tertiary structure is imparted upon the binding of p16 to CDK4.Keywords: analytical ultracentrifugation; ankyrin-like repeat; cyclin; circular dichroism; cyclin dependent kinase inhibitor Control of the eukaryotic cell cycle is a highly regulated process that involves the interaction of a large number of macromolecules. Critical checkpoints in this process are found during the entry of cells into both the GUS and G2/M phases of the cell cycle (for reviews, see Draetta, 1994;Sherr, 1995). The cyclin-dependent kinases (CDKs) are enzymes whose activities govern these checkpoints. CDK holoenzymes, which consist of a CDK catalytic subunit and a cyclin regulatory subunit, are regulated, in part, by their temporal expression, degradation, phosphorylation, and dephosphorylation. This regulation throughout the cell cycle serves to drive the cell through the successive phases.Recent studies have identified CDK inhibitors, a new class of proteins, adding yet another level of control to CDK regulation (for review, see Elledge & Harper, 1994). These CDK inhibitors are thought to function by blocking and/or disrupting CDK-cyclin association. p16, one of the first of these inhibitors to be discovered, was originally cloned from a yeast-two hybrid interaction screen using CDK4 as the bait protein (Serrano et al., 1993).

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Mlab — A mathematical modeling tool

Cited by 383 publications

References 6 publications

Volume-regulatory responses of Amphiuma red cells in anisotonic media. The effect of amiloride.

Volume-regulatory responses of Amphiuma red cells in anisotonic media. The effect of amiloride.

Structural and Functional Insights into Intramolecular Fructosyl Transfer by Inulin Fructotransferase

Structural characterization of the tumor suppressor p16, an ankyrin‐like repeat protein

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