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BACKGROUND Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an inherited lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme required for stepwise degradation of keratan sulfate (KS). We have developed a selective, sensitive, accurate and precise LC-MS/MS assay for the KS-derived disaccharides(More)
Plasmodium falciparum is unable to synthesize purine bases and relies upon purine salvage and purine recycling to meet its purine needs. We report that purines formed as products of polyamine synthesis are recycled in a novel pathway in which 5'-methylthioinosine is generated by adenosine deaminase. The action of P. falciparum purine nucleoside(More)
The structure of the polysaccharide isolated from tetrasporophytic plants of the New Zealand red alga Gigartina decipiens has been determined by chemical and spectroscopic techniques. It is a linear polymer composed primarily of alternating 3-linked beta-D-galactopyranosyl 2-sulphate and 4-linked alpha-D-galactopyranosyl 2,6-disulphate residues. About 15%(More)
A polysaccharide rich in 4',6'-O-(1-carboxyethylidene)-substituted (i.e., pyruvylated) beta-carrageenan has been prepared by solvolytic desulfation of a polysaccharide containing predominantly pyruvylated alpha-carrageenan, which was extracted from the red seaweed, Callophycus tridentifer. The 13C and 1H NMR chemical shifts of pyruvylated beta-carrageenan(More)
Immucillin-H [ImmH; (1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol] is a 23 pM inhibitor of bovine purine nucleoside phosphorylase (PNP) specifically designed as a transition state mimic [Miles, R. W., Tyler, P. C., Furneaux, R. H., Bagdassarian, C. K., and Schramm, V. L. (1998) Biochemistry 37, 8615-8621]. Cocrystals of PNP and the(More)
Transition state structures can be derived from kinetic isotope effects and computational chemistry. Molecular electrostatic potential maps of transition states serve as blueprints to guide synthesis of transition state analogue inhibitors of target enzymes. 5'- Methylthioadenosine phosphorylase (MTAP) functions in the polyamine pathway by recycling(More)
Escherichia coli 5'-methylthioadenosine/S-adenosyl-homocysteine nucleosidase (MTAN) hydrolyzes its substrates to form adenine and 5-methylthioribose (MTR) or S-ribosylhomocysteine (SRH). 5'-Methylthioadenosine (MTA) is a by-product of polyamine synthesis and SRH is a precursor to the biosynthesis of one or more quorum sensing autoinducer molecules. MTAN is(More)
Genetic defects in human purine nucleoside phosphorylase cause T-cell deficiency as the major phenotype. It has been proposed that efficient inhibitors of the enzyme might intervene in disorders of T-cell function. Compounds with features of the transition-state structure of purine nucleoside phosphorylase were synthesized and tested as inhibitors. The(More)
Transition states can be predicted from an enzyme's affinity to related transition-state analogues. 5'-Methylthioadenosine nucleosidases (MTANs) are involved in bacterial quorum sensing pathways and thus are targets for antibacterial drug design. The transition-state characteristics of six MTANs are compared by analyzing dissociation constants (K(d)) with a(More)