Inosine crystal structure

Cyclic Dimer Configurations. In 8-bromoinosine [BRINOSlOj the inosine residues are self-associated (Fig. 17.8 a). This is a rare example of self-association in the crystal structures of the nucleosides. Surprisingly, in uridine [BEURID10] (Fig. 17.8b) the CH- 0=C hydrogen bond plays the same role as the NH 0=C interaction in 8-bromoinosine. 

The purine nucleoside crystal structures adenosine, inosine, and guanosine provide less reliable data from the hydrogen-bonding point of view. This is particularly true of the guanosines, where only four structures can be reported. 

Selected crystal structures of adenosine, guanosine, inosine and their derivatives. In adenosine [ADENOSIO], the hydrogen-bond structure involves all func-... 

In inosine, the NH2 at C(2) on guanine is removed, thereby reducing the hydrogen-bonding capability by a donor group with two functional hydrogens. 8-Bromoinosine is a rare example where the self-association of the purine residues occurs in the crystal structure of a nucleoside. 

F. M. McMillan, M. Gaboon, A. White, L. Hedstrom, G.A. Petsko, and D. Ringe. 2000. Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5 -monophosphate dehydrogenase Evidence of a substrate-induced hinged-lid motion by loop 6 Biochemistry 39 4533-4542. (PubMed)... 

X-ray crystal structures of the beef purine nucleoside phosphorylase enzyme with a substrate-analogue complex (inosine and the non-nucleophilic sulfate), a transition state-analogue complex (immucillin H and phosphate) and a product complex (inosine and ribose-l-phosphate) led to the conclusion that most atomic motion was in the anomeric centre, which swung from attachment to... 

Another enzyme for which X-ray diffraction studies have aided in an analysis of the mode of action is the enzyme dihydrofolate reductase. This catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate, an essential coenzyme used in the synthesis of thymidylate, inosinate, and methionine. The antitumor agent methotrexate is a powerful inhibitor of dihydrofolate reductase, causing, on binding, a cellular deficiency of thymidylate (the cause of its antitumor activity). The crystal structures of the enzyme from two bacterial sources—Escherichia coli and Lactobacillus casei—and from chicken liver have been studied (88-90). Both the E. coli and L casei enzymes have been studied as complexes with methotrexate bound at the active site, and, in the case of the . casei enzyme, the cofactor, NADPH, was also present. 

Purine nucleoside phosphorylase (PNP). In contrast to lU-NH, PNP appears to use extensive contacts with the purine ring to promote catalysis and relatively few contacts with the ribosyl ring. The crystal structure of PNP has been determined in a complex with an iminosugar inhibitor, immucillin H, which was developed based on TS analyses of PNP-catalyzed hydrolysis and arsenolysis reactions. TS analysis revealed that the enzyme catalyzes a dissociative A Dn mechanism. The crystal structure was compared with the structures determined by Ealick and coworkers ° of PNP in a Michaelis complex analogue, PNP-inosine-sulfate, and a product complex, PNP-a-D-ribose-l-phosphate-hypoxanthine. 

TS analysis of inosine arsenolysis. TS analysis was performed on the arsenolysis of inosine under steady state conditions. The primary, KIE was near the lower limit (1.025-1.029) calculated for an AnDn mechanism with adenosine and could indicate either an AnDn or Dn An mechanism. The large a- and j8-secondary KIEs indicated a transition state with high oxocarbenium ion character. Analysis of X-ray crystal structures of PNP demonstrates that there is not enough space in the enzyme active site between the leaving group purine and the phosphate nucleophile to allow formation of a stable oxocarbenium ion (see Section 3). Thus, the most likely mechanism for arsenolysis is an extremely dissociative AnDn mechanism. The primary, 9- N KIE = 1.010 was lower than expected, as discussed below. 

FIGURE 25.15 (a) Structure of a tRNA isolated from yeast that has the speoifio function of transferring alanine residues. Transfer RNAs often oontain unusual nuoleosides. PSU = pseudouridine, RT = ribothymidine, Ml = 1 -methylinosine, I = inosine, DMG = A/ -methylguanosine, DHU = 4,5-dihydrouridine, 1 MG = 1 -methylguanosine. (b) The X-ray crystal structure of a phenylalanine-... 

Finally, an interesting paper by Tokdemir and Nelson looks at irradiated inosine single crystals [87], The authors have used calculations on the anisotropic hyperfine couplings as an aid in identifying free radical structures. They find that the computed dipolar coupling eigenvectors correlate well with the experimental results. The input Cartesian coordinates used for the calculations were obtained from the crystallographic data. 

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