A common theme in the amino acid sequences of actin and many actin-binding proteins?

The amino acid sequences of several actin regulatory proteins have recently been determined. Do these proteins function by mimicking actin-actin interaction sites?     

Do myc,fos and E1A function as protein phosphatase inhibitors?

The oncogenic proteins myc, fos and E1A bear striking resemblance to protein phosphatase inhibitors 1 and 2. Both sets of proteins possess several regions rich in proline (P), glutamic acid (E), serine (S) and threonine (T). In addition to PEST sequences four of the five proteins contain clusters of arginine-arginine pairs. On the basis of these similarities, I suggest that myc, fos and E1A are protein phosphatase inhibitors.     

Do the hairpin and VS ribozymes share a common catalytic mechanism based on general acid–base catalysis? A critical assessment of available experimental data

The active centers of the hairpin and VS ribozymes are both generated by the interaction of two internal loops, and both ribozymes use guanine and adenine nucleobases to accelerate cleavage and ligation reactions. The centers are topologically equivalent and the relative positioning of key elements the same. There is good evidence that the cleavage reaction of the VS ribozyme is catalyzed by the guanine (G638) acting as general base and the adenine (A756) as general acid. We now critically evaluate the experimental mechanistic evidence for the hairpin ribozyme. We conclude that all the available data are fully consistent with a major contribution to catalysis by general acid-base catalysis involving the adenine (A38) and guanine (G8). It appears that the two ribozymes are mechanistically equivalent.     

Hormone studies inMyxine glutinosa: effects of the eicosanoids arachidonic acid,prostaglandin E1, E2, A2, F2α, thromboxane B2 and of indomethacin on plasma cortisol,blood pressure,urine flow and electrolyte balance

Summary Hagfish,Myxine glutinosa, were used in an investigation of the possible effects of various eicosanoids and the prostaglandin synthetase inhibitor indomethacin, on cortisol production, blood pressure control, urine flow and electrolyte balance.Cortisol levels in plasma of untreated control animals and plasma from animals 1 h following injection of 50 g kg^–1 prostaglandin E₁, E₂, A₂, F₂ TXB₂ and indomethacin were not detectable. However, plasma cortisol levels rose to between 10 and 26 pg ml^–1 1 h following injection of either 50 g kg^–1 arachidonic acid or prostaglandin E₂. This rise was similar in magnitude to that produced 1 h following administration of 50 g kg^–1 porcine ACTH.The resting dorsal aortic blood pressure of between 3.50 and 3.75 mmHg was reduced on average by 50% for 12–15 min when animals received 10 g kg^–1 arachidonic acid, prostaglandin E₁, E₂, A₂, and TXB₂ and was effectively reduced to zero for 20 min or more following 50 g kg^–1 of these eicosanoids. Similar doses of prostaglandin F₂, however, evoked an increase in blood pressure (19–33%) whilst indomethacin was without effect.Control measurements of urine flow inMyxine were estimated to be between 540 and 660 l h^–1 kg^–1. There was a marked reduction in urine output following the arterial vasodepression induced by arachidonic acid, prostaglandin E₁, E₂, A₂ and TXB₂ in doses of 10 g kg^–1, an effect which became even more pronouced following injection of 50 g kg^–1 quantities, leading in some cases to complete anuria. There was no significant change in urine volume following either the vasopressor action of prostaglandin F₂ or following indomethacin.None of the compounds tested in this study significantly influenced the plasma or urine electrolyte status ofMyxine.     

Pt(II) complexes with (N,N′) or (C,N,E)− (E = N,S) ligands: Cytotoxic studies,effect on DNA tertiary structure and structure–activity relationships

The cytotoxic activity of two series of platinum(II) complexes containing the polyfunctional imines R¹–CHN–R² [R¹ = phenyl or ferrocenyl unit and R² = (CH₂)_n–CH₂–NMe₂ where n = 1 or 2) (1 and 2) or C₆H₄-2-SMe (3)] acting as a bidentate (N,N′) (4–7) or terdentate [C(phenyl or ferrocenyl),N,N′]^? (8–10) or [C(ferrocenyl),N,S]^? ligand (11) in front of A549 lung, MDA-MB231 breast and HCT116 colon human adenocarcinoma cell lines is reported. The results reveal that most of the platinum(II) complexes are active against the three assayed lines and compounds 6, 7 and the platinacycles 10 and 11 exhibit a remarkable antiproliferative activity, even greater than cisplatin itself, in the cisplatin resistant HCT116 human cancer cell line. Electrophoretic DNA migration studies showed that most of them modify the DNA tertiary structure in a similar way as the reference cisplatin. Solution studies of a selection of the most relevant complexes have also been performed in order to test: (a) their stability in the aqueous biological medium and/or the formation of biologically active species and (b) their proclivity to react with 9-methylguanine (9-MeG), as a model nucleobase. Computational studies at DFT level have also been performed in order to explain the different solution behaviour of the complexes and their proclivity to react with the nucleobase.     

In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. II: mRNA for PGF2α, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue

Previously, it was reported that chronic intra-uterine infusion of PGE(1) or PGE(2) every 4h inhibited luteolysis in ewes by altering luteal mRNA for luteinizing hormone (LH) receptors and unoccupied and occupied luteal LH receptors. However, estradiol-17β or PGE(2) given intra-uterine every 8h did not inhibit luteolysis in cows, but infusion of estradiol+PGE(2) inhibited luteolysis. In contrast, intra-luteal implants containing PGE(1) or PGE(2) in Angus or Brahman cows also inhibited the decline in circulating progesterone, mRNA for LH receptors, and loss of unoccupied and occupied receptors for LH to prevent luteolysis. The objective of this experiment was to determine how intra-luteal implants of PGE(1) or PGE(2) alter mRNA for prostanoid receptors and how this could influence luteolysis in Brahman or Angus cows. On day-13 Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE(1), or PGE(2) and corpora lutea were retrieved on day-19. Corpora lutea slices were analyzed for mRNA for prostanoid receptors (FP, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4) by RT-PCR. Day-13 Angus cow luteal tissue served as pre-luteolytic controls. mRNA for FP receptors decreased in day-19 Vehicle controls compared to day-13 Vehicle controls regardless of breed. PGE(1) and PGE(2) up-regulated FP gene expression on day-19 compared to day-19 Vehicle controls regardless of breed. EP1 mRNA was not altered by any treatment. PGE(1) and PGE(2) down-regulated EP2 and EP4 mRNA compared to day-19 Vehicle controls regardless of breed. PGE(1) or PGE(2) up-regulated mRNA EP3B receptor subtype compared to day-19 Vehicle control cows regardless of breed. The similarities in relative gene expression profiles induced by PGE(1) and PGE(2) support their agonistic effects. We conclude that both PGE(1) and PGE(2) may prevent luteolysis by altering expression of mRNA for prostanoid receptors, which is correlated with changes in luteal mRNA for LH receptors reported previously in these same cows to prevent luteolysis.     

A B3LYP and MP2(full) theoretical investigation into the cooperativity effect between dihydrogen-bonding and H–M∙∙∙π (M = Li, Na, K) interactions among HF, MH with the π-electron donor C2H2, C2H4 or C6H6

The DFT-B3LYP/6-311++G(3df,2p) and MP2(full)/6-311++G(3df,2p) calculations were carried out on the binary complex formed by HM (M?=?Li, Na, K) and HF or the π-electron donor (C₂H₂, C₂H₄, C₆H₆), as well as the ternary system FH???HM???C₂H₂/C₂H₄/C₆H₆. The cooperativity effect between the dihydrogen-bonding and H–M???π interactions was investigated. The result shows that the equilibrium distances R _H???H and R _M???π in the ternary complex decrease and both the H???H and H–M???π interactions are strengthened when compared to the corresponding binary complex. The cooperativity effect of the dihydrogen bond on the H–M???π interaction is more pronounced than that of the M???π bond on the H???H interaction. Furthermore, the values of cooperativity effect follow the order of FH???HNa???π?>?FH???HLi???π?>?FH???HK???π and FH???HM???C₆H₆?>?FH???HM???C₂H₄?>?FH???HM???C₂H₂. The nature of the cooperativity effect was revealed by the analyses of the charge of the hydrogen atoms in H???H moiety, atom in molecule (AIM) and electron density shifts methods.