Purine binding

The P-site of adenylyl cyclase inhibits cyclic AMP accumulation. Since P, and P2 receptors are located on the cell surface, they bind purines or pyrimidines in the extracellular space. There also is an adenosine binding site located intracellularly on the enzyme adenylyl cyclase (see Ch. 21). This is referred to as the P-site of adenylyl cyclase. Binding of adenosine and other purines, notably 3 AMP, 2 deoxy-3 -ATP and 2, 5 -dideoxyadenosine to this site, inhibits adenylyl cyclase activity [8]. The P-site of adenylyl cyclase and other intracellular purine binding sites are not classified as purinergic receptors. 

In comparison to butyric acid, the microenvironment of the carboxylic acid in 49 alters its complexation efficiency and the preferred geometry of its adenine complex. The nucleoside selectivity is also altered and improved to the extent that 49 can be considered a moderately selective host. As seen in Table 6 (entries 8-11), 49 selectively binds purines, with the association constants following the order A (56) > G (57) > (58) C Si (59) U. The maximum selectivity is AAG° = 2.8 kcal mol-1, while for butyric acid the selectivity was MejG Si C A U with only 1.3 kcal mol-1 separating the strongest and weakest complexes [52],... 

DEAE-celluIose with CaS04 binder in HCI or in ammonia changes separation by binding purines in particular, whether as the base or the nucleoside. 

Although the exact functions of each component subunit are as yet poorly defined, the second largest subunit (B150, the rpbZ gene product) of yeast RNA Pol II contains sequences implicated in binding purine nucleotides and a Zn ion. 

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... 

FIGURE 16.8 (a) Phosphoglycolohydroxamate is an analog of the enediolate transition state of the yeast aldolase reaction, (b) Purine riboside, a potent inhibitor of the calf intestinal adenosine deaminase reaction, binds to adenosine deaminase as the 1,6-hydrate. The hydrated form of purine riboside is an analog of the proposed transition state for the reaction. 

Binding of cisplatin to the neighbouring bases in the DNA disrupts the orderly stacking of the purine bases when it forms a 1,2-intrastrand crosslink, it bends the DNA helix by some 34° towards the major groove and unwinds the helix by 13°. These cross-links are believed to block DNA replication. 

Nuclear factor kappa B (NF-kB) is the generic term for a family of dimeric eukaryotic transcription factors, composed of members of the Rel family of DNA-binding proteins including the mammalian proteins RelA (or p65), cRel, RelB, p50 and p52, and the Drosophila proteins Dorsal, Dif and Relish. These proteins bind with different affinities to a consensus DNA sequence motif (called the kB site) consisting of the sequence 5 -GGGRNNYYCC-3 in which R is a purine, Y is a pyrimidine, and N is any base. 

PNA targeting of duplex DNA is not limited to homopurine sequences. Under special circumstances (high negative superhelical stress) mixed purine-pyrimidine PNA-peptide conjugates can bind by duplex invasion (Fig. 4.7) [31], but such complexes are of limited stability. However, using a set of pseudo-complementary PNAs containing diaminopurine-thiouracil substitutions, very stable double duplex invasion complexes can be formed (Fig. 4.4) and the only sequence requirement is about 50% AT content. Very recently, it was also demonstrated that reasonably stable helix invasion complexes can be obtained with tail-clamp PNA comprising a short (>six bases) homopyrimidine bis-PNA clamp and a mixed sequence tail extension [32] (Fig. 4.7). 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

The process of RNA synthesis in bacteria—depicted in Figure 37-3—involves first the binding of the RNA holopolymerase molecule to the template at the promoter site to form a PIC. Binding is followed by a conformational change of the RNAP, and the first nucleotide (almost always a purine) then associates with the initiation site on the 3 subunit of the enzyme. In the presence of the appropriate nucleotide, the RNAP catalyzes the formation of a phosphodiester bond, and the nascent chain is now attached to the polymerization site on the P subunit of RNAP. (The analogy to the A and P sites on the ribosome should be noted see Figure... 

The association between RNase A and 3 -UMP or 3 -dUMP has been studied by P n.m.r. and kinetic methods, respectively. In both cases the participation of two dissociable groups at the active site of the enzyme was demonstrated, in agreement with n.m.r. and A -ray - studies on the binding of 3 -CMP to RNase. In the binding of Tj RNase to purine nucleotide monophosphates, the phosphate group appears to have an important effect while the ribose ring is relatively unimportant. ... 

Nucleobases, including 9-methyl-, 9-ethyl-, 1,9-dimethyl-guanine and 2-amino-6-methoxy-9-methylpurine, form complexes of the type Au(N)Cl3 when reacted with [AuCU] in water at pH 3—4. Binding of a AuCh unit to the N (7) position of the purine ring was confirmed by X-ray crystallography [26]. 

For the purines, only in the case of adenine has the [N3 + N9] bridging mode been observed (76-78). This further highlights the difference in binding patterns between the N3 of A and G. A recent example is seen in the Pd2-adenine complex, 18, formed in reactions of 19 with... 

There have been few reports of purine derivatives1 that contain metal-carbon nucleobase binding (75), and those that have been described are often polymetalated (84). Quite recently mononuclear complexes of adenine and guanine have been prepared that contain... 

Patients with tumor lysis syndrome experience a wide range of metabolic abnormalities. The massive cell lysis that occurs leads to the release of intracellular electrolytes, resulting in hyperkalemia and hyperphosphatemia. High concentrations of phosphate bind to calcium, leading to hypocalcemia and calcium phosphate precipitation in the renal tubule. Purine nucleic acids are also released that are subsequently metabolized to uric acid... 

Regular pyrimidines are less effective ligands for Ni11 ions. They may use, inter alia, their C=0 donor to yield monodentate coordination.1835 Insertion of a sulfur atom into a pyrimidine moiety increases considerably its binding ability.1836 Thiolation of uridine at C(2) or C(4) results in formation of a quite effective S,N3 four-membered chelate in the complexes with Ni11. Thiolation of purine at C(6) increases the stability constant by 3.5 orders of magnitude. 

Most in vitro studies of xanthines have centered around the enzyme xanthine oxidase. Bergmann and co-workers 40-4)) have examined the main oxidative pathways in the xanthine oxidase catalyzed oxidation of purines. The mechanism proposed by these workers 41 > is that the enzyme binds a specific tautomeric form of the substrate, regardless of whether or not that form represents the major structure present in solution. It is then proposed that the purine, e.g., xanthine, undergoes hydration at the N7=C8 double bond either prior to or simultaneously with dehydrogenation of the same position. Accordingly, the process would involve either pathway a or b. Fig. 15. Route a would give a lactim form of the oxidized purine, while b would give the cor-... 

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