Hypoxanthine, 8- -, crystal structure

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) ... 

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... 

The problem may and has been considered also in relation to the crystal structure of other purines, although in somewhat less detail.173 Recent findings indicate that although the crystals of guanine, hypoxanthine, and 8-azaguanine contain the N(9)H tautomer of the bases,174 175 the crystal of 6-mercaptopurine monohydrate is made of the N(7)H form.176 177... 

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. 

A variant on electrophile migration is suggested for the hydrolysis reaction, based on several lines of evidence (1) PNP can form exceptionally tight interactions with hypoxanthine (Kd = 1.3 pM) (2) there are many contacts with the phosphate nucleophile in the crystal structures which orient and activate anionic phosphate through its negatively charged oxygen atoms and increase the reaction rate 100-fold ... 

The crystal structure of hypoxanthine phosphoribosyltransferase has been solved in a ternary complex of the enzyme with the substrate 5-phosphoribosyl 1-pyrophosphate (PRPP) and an analogue of hypoxanthine with a carbon atom in place of As with PNP and OPRTase, these structures showed many contacts with... 

Somoza JR, Chin MS, Focia PJ et al. Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from the protozoan parasite Tritrichomonas foetus. Biochemistry 1996 35(22) 7032-7040. 

Focia PJ, Ciaig Illrd SP, Nieves-Alicea R et al. A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransforase of Trypanosoma cruzi. Biochemistry 1998 37 43) 15066-15075. 

Sakore TD, Sobell HM (1969) Crystal and molecular structure of a hydrogen-bonded complex containing adenine and hypoxanthine derivatives 9-ethyl-8-bromoadenine 9-eth-yl-8-bromohypoxanthine. J Mol Biol 43 77-87... 

Very little structural information is available for cadmium(II) complexes with neutral oxopurines. Nevertheless, the basicity of the N-donors in this kind of oxopurine ligand, as well as the softness, increases after the dissociation of at least one of the protons. Consequently, most of the available crystal data concerning complexes of such ligands refer to the tmivalent anions of hypoxanthine (Hhyp), xanthine (Hxan) or theophylline (Htheo). Neutral hypoxanthine yields the compound [Cd2(p2-N3,N9-H(N7)hyp)2(p2 H20)2(S04)2(H20)2] [27], in which the... 

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