Adenylates

The first technique is very intuitive. Out of the few proteins that could be crystallized in a number of different conformations, adenylate kinase is probably the best-studied example. By combining nine observed crystal structures and interpolating between them, a movie was constructed that visualized a hypothetical path of its hinge-bending transition (jVonrhein et al. 1995]). 

To facilitate conformational transitions in the before-mentioned adenylate kinase, Elamrani and co-workers scaled all atomic masses by a large factor thus allowing the use of a high effective simulation temperature of 2000K ([Elamrani et al. 1996]). To prevent protein unfolding, elements of secondary structure had to be constrained. 

Elamrani et al. 1996] Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A. Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics Adenylate Kinase as a Test Case. Proteins 25 (1996) 79-88 [Elcock et al. 1997] Elcock, A.H., Potter, M.J., McCammon, J.A. Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In Computer Simulation of Biomoleeular Systems, Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., Leiden... 

Adenoviridae Adenovirus, type 2 Adenylate cyclase Adenyl cyclase O-Adenylylation Adenylyl cyclase... 

Brain adenylate cyclase Brain imaging Brains Brake bands Brake blocks Brake facings Brake fluids... 

Luciferin (41) (R = H) reacts with adenosiae triphosphate (ATP) and the en2yme to give a complex (42) of the adenylate ester (41) R =... 

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

Two AT-II receptors, AT and AT2 are known and show wide distribution (27). The AT receptor has been cloned and predominates ia regions iavolved ia the regulation of blood pressure and water and sodium retention, eg, the aorta, Hver, adrenal cortex, and ia the CNS ia the paraventricular nucleus, area postrema, and nucleus of the soHtary tract. AT2 receptors are found primarily ia the adrenal medulla, utems, and ia the brain ia the locus coeruleus and the medial geniculate nucleus. AT receptors are GCPRs inhibiting adenylate cyclase activity and stimulating phosphoHpases C, A2, and D. AT2 receptors use phosphotyrosiae phosphatase as a transduction system. 

Opiates iateract with three principal classes of opioid GPCRs )J.-selective for the endorphiQS,5-selective for enkephalins, and K-selective for dynorphias (51). AU. three receptors have been cloned. Each inhibits adenylate cyclase, can activate potassium channels, and inhibit A/-type calcium channels. The classical opiates, morphine and its antagonists naloxone (144) and naltrexone (145), have moderate selectivity for the. -receptor. Pharmacological evidence suggests that there are two subtypes of the. -receptor and three subtypes each of the 5- and K-receptor. An s-opiate receptor may also exist. 

Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide. Vasoactive intestinal peptide (VIP)... 

J (339), a 28-amino acid peptide, is a member of a family of stmctuially related peptides that includes secretin [1393-25-5] (340), growth hormone releasing factor (GRF), and pituitary adenylate cyclase-activating peptide (PACAP) [137061(341) (83). 

Lithium. In the lithium carbonate treatment of certain psychotic states, a low incidence (3.6%) of hypothyroidism and goiter production have been observed as side effects (6,36) (see Psychopharmacologicalagents). It has been proposed that the mechanism of this action is the inhibition of adenyl cyclase. Lithium salts have not found general acceptance in the treatment of hyperthyroidism (see Lithiumand lithium compounds). 

Resistance to Lincomycin. Resistance to lincomycin is developed slowly, and is usually caused by modification of 23S ribosomal RNA, which leads to co-resistance to macroHde, lincosaminide, and streptogramin B antibiotics (25). Inactivation of lincomycin by clinical isolates of strains of Staphjlococcus aureus and Staphjlococcus haemoljticus, though retention of sensitivity to macroHdes (see Antibiotics, macrolides) and streptogramins (see Antibiotics, peptides), has been found to be the consequence of the conversion of the antibiotic into its 3-(5 -adenylate) (26). 

Cross-resistance between lincomycin and clindamycin is complete (64), and co-resistances of lincomycin also apply to clindamycin. However, the inactivation of clindamycin by clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus is caused by adenylylation at the 4-position to form clindamycin 4-(5 -adenylate) [29752-38-3] (7) in contrast to the lincomycin 3-(5 -adenylate) [117785-83-8] (8) that forms (26). 

Clindamycin 3-phosphate [28708-34-17, antibacterially inactive in vitro, and the ribonucleotides clindamycin 3-(5 -cytidylate) [31186-90-0], clindamycin 3-(5 -adenylate) [31186-91-1], clindamycin 3-(5 -uridylate) [36010-69-2], and clindamycin 3-(5 -guanylate) [36010-70-5], all inactive in vitro, can be generated... 

Forskolin (5-[acetyloxy]-3-ethenyldodecahydro-6,10,10b-trihydroxy-3,4a,7,7,10a-penta-methyl-[3R- 3a-4aP, SP, 6P, 6aa,10a, lOaP, 10ba -lFf-naphtho[2,l-b]pyran-l-one) [66575-29-9] M 410.5, m 229-232°, 228-233°. Recrystd from CfiH6-pet ether. It is antihypertensive, positive ionotropic, platelet aggregation inhibitory and adenylate cyclase activating properties [Chem AbstrS9 1978 244150, de Souza et al. Med Res Rev 3 201 1983]. 

Adenosine-3 -monophosphoric acid hydrate [3 -adenylic acid, 3 -AMP] [84-21-9] M 347.3, m 197°(dec, as 2H2O), 210°(dec), m 210°(dec), [a]s46 -50° (c 0.5, 0.5M Na2HP04), pK 3.65, pKz 6.05. It crystallises from large volumes of H2O in needles as the monohydrate, but is not very soluble in boiling H2O. Under acidic conditions it forms an equilibrium mixture of 2 and 3 adenylic acids via the 2, 3 -cyclic phosphate. When heated with 20% HCl it gives a quantitative yield of furfural after 3hours, unlike 5 -adenylic acid which only gives traces of furfural. The yellow monoacridine salt has m 175°(dec) and... 

Figure 4.14 Examples of different types of open twisted a/p structures. Both schematic and topological diagrams are given. In the topological diagrams, arrows denote strands of p sheet and rectangles denote a helices, (a) The FMN-binding redox protein flavodoxln. (b) The enzyme adenylate kinase, which catalyzes the reaction AMP +...

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