Hypoxanthine structure

Therapeutic Function Cardiotonic Chemical Name 9-/3-D-ribofuranosylhypoxanthine Common Name Hypoxanthine riboside Structural Formula ... 

The molyhdopterin cofactor, as found in different enzymes, may be present either as the nucleoside monophosphate or in the dinucleotide form. In some cases the molybdenum atom binds one single cofactor molecule, while in others, two pterin cofactors coordinate the metal. Molyhdopterin cytosine dinucleotide (MCD) is found in AORs from sulfate reducers, and molyhdopterin adenine dinucleotide and molyb-dopterin hypoxanthine dinucleotide were reported for other enzymes (205). The first structural evidence for binding of the dithiolene group of the pterin tricyclic system to molybdenum was shown for the AOR from Pyrococcus furiosus and D. gigas (199). In the latter, one molyb-dopterin cytosine dinucleotide (MCD) is used for molybdenum ligation. Two molecules of MGD are present in the formate dehydrogenase and nitrate reductase. 

Xanthine dehydrogenase that mediates the conversion of hypoxanthine into xanthine and uric acid has been studied extensively since it is readily available from cow s milk. It has also been studied (Leimkiihler et al. 2004) in the anaerobic phototroph Rhodobacter capsulatus, and the crystal structures of both enzymes have been solved. Xanthine dehydrogenase is a complex flavoprotein containing Mo, FAD, and [2Fe-2S] redox centers, and the reactions may be rationalized (Hille and Sprecher 1987) ... 

C222x Z = 4 Dx = 1.82 R = 0.061 for 3,313 intensities. The structure is isomorphous with the monosodium salt of 5 -IMP.184 The structure is a nonstoichiometric complex (—86% Pt occupancy). The 5 -IMP molecules (86% occupancy) liganded to the Pt exist as dianions, whereas the 5 -IMP molecules (0.14% occupancy) not involved in Pt coordination are monoprotonated (5 -IMPH). The coordination about the Pt atom is approximately square-planar two of the ligands are the N-7 atoms of the hypoxanthine base and the two ammonia molecules. In fact, the Pt atom... 

P5. Patel, P. I., Caskey, C. T., and Chinault, C. A., Fine structure of the human hypoxanthine guanine phosphoribosyltransferase gene. Mol. Cell. Biol. 6,393-403 (1986),... 

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

Hypoxanthine and copper chloride in aqueous HCl at pH 4 form [Cu2(HxH2)4Cl2]2Cl2 6H2O (41) (70AX(B)1609), the X-ray structure of which is similar to its AdH analog 40. 

The purine ring-numbering scheme, 1, and structures of some simple purines, viz. adenine 2, guanine 3, caffeine 4, theophylline 5, adenosine 6, 2 -deoxyadenosine 7, guanosine 8, 2 -deoxyguanosine 9, xanthine 10, and hypoxanthine 11, are shown. 

The structure of allopurinol, an isomer of hypoxanthine, is shown in Figure 36-7. 

RGURE 22-47 Allopurinol, an inhibitor of xanthine oxidase. Hypoxanthine is the normal substrate of xanthine oxidase. Only a slight alteration in the structure of hypoxanthine (shaded pink) yields the medically effective enzyme inhibitor allopurinol. At the active site, allopurinol is converted to oxypurinol, a strong competitive inhibitor that remains tightly bound to the reduced form of the enzyme. 

The first surprise was that these molecules are much longer than seems necessary for the formation of adapters. In addition, 10-20% of their bases are modified greatly from their original form.171 Another surprise was that the anticodons are not all made up of "standard" bases. Thus, hypoxanthine (whose nucleoside is inosine) occurs in some anticodons. Conventional "cloverleaf" representations of tRNA, which display their secondary structures, are shown in Figs. 5-30 and 29-7. However, the molecules usually have an L shape rather than a cloverleaf form (Figs. 5-31 and 29-6),172 and the L form is essential for functioning in protein synthesis as indicated by X-ray and other data.173 Three-dimensional structures, now determined for several different tRNAs,174 175 are all very similar. Structures in solution are also thought to be... 

In the case of guanine derivatives (80), coordination to the 0-6 atom may also be possible. In fact this has only rarely been observed.146,147,154 Coordination at N-3 is sterically hindered, whereas binding at the NH2 group is rare and binding at N-l can only occur after deprotonation in an alkaline medium.146,147,155 Coordination of guanines and hypoxanthines (80, but with the NH2 replaced by hydrogen) takes place almost universally at the N-7 position, as proved by numerous crystal structures, unless N-7 is blocked.155... 

Until recently the lactol ring structure of 2-desoxy-D-ribose in nucleic acid had been proved conclusively only for the thymidine nucleoside component and in this case it was furanose in form.26 Subsequently Brown and Lythgoe,27 by application of the periodate oxidation procedure to the 2 -desoxy ribosides of guanine, hypoxanthine, cytosine and thymine, afforded proof of the presence of a furanose sugar in each compound. 

Batey, R. T., Gilbert, S. D., and Montange, R. K. (2004). Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine. Nature432, 411-415. 

Solid sodium nitrite (0.97 g) was added at room temperature with stirring over a period of one hour to a solution of 2-chloro-9-(2-hydroxyethoxymethyl)adenine (0.5 g) in glacial acetic acid (10 ml). The reaction mixture was stirred for an additional 41/2 hours. The white solid was removed by filtration, washed with cold acetic acid and then well triturated with cold water to remove the sodium acetate present. The solid product was retained. The combined acetic acid filtrate and wash was evaporated at reduced pressure and 40°C bath temperature and the residual oil triturated with cold water. The resulting solid material was combined with the previously isolated solid and the combined solids dried and recrystallized from ethanol to give 2-chloro-9-(2-hydroxyethoxymethyl)-hypoxanthine (0.25 g), MP>310°C. Elemental analysis and NMR spectrum were consistent with this structure. 

The lactam-lactim, tautomerism, of hydroxypurines illustrated, for example, for hypoxanthine by the structures 8 and 9. 

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