Molybdopterin biosynthesis

K. V. Investigation of the early steps of molybdopterin biosynthesis in Escherichia coli through the use of in vivo labelling studies, J. Biol. Chem. 

K V. Mechanistic and mutational studies of Escherichia coli molybdopterin synthase clarify the final step of molybdopterin biosynthesis,... 

Appleyard, M. V., Sloan, J., Kana n, G. J., Heck, I. S., Kinghorn, J. R., and Unkles, S. E. The Aspergillus nidulans cnxF gene and its involvement in molybdopterin biosynthesis. Molecular characterization and analysis of in vivo generated mutants, J Biol Chem 1998, 273, 14869-14876. 

Genetic defects of molybdopterin biosynthesis (Fig. 3) also result in severe neurologic and developmental deflcits (74). Genetic defects in the biosynthesis of the quinine-type coenzyme QIO (97, Fig. 11) can result in encephalopathy, myopathy, and renal disease (53). 

Molybdate-uptake genes and molybdopterin-biosynthesis genes on a bacterial plasmid-characterization of MoeA as a filament-forming protein with adenosine triphosphatase activity. Fur J Biochem 250 524-531. 

The biosynthesis of molybdopterin has been investigated using double labeling experiments using labeled... 

What is known about the biosynthesis of MPT and the MPT dinucleotides has been reviewed elsewhere from both a biochemical and a genetic perspective [7,8,62-64], Here we only discuss the hnal steps in MPT biosynthesis, which involve the enzyme molybdopterin synthase [65,66],... 

However, the sheer complexity of a pathway is not an indicator for the vitamin status of a given class of compounds, as opposed to endogenous biosynthesis in mammals. Thus, animals biosynthesize molybdopterin, which is a cofactor involved in certain redox reactions, from basic building blocks using at least... 

The persulfide intermediate 2 can also serve as a sulfur source for the biosynthesis of thiamine (6), lipoic acid (7), molybdopterin (8), and biotin (9) (Fig. 1). 

Even though E. coli is a very well-studied bacterium, many interesting mechanistic problems in cofactor biosynthesis in this organism remain unsolved. The mechanisms for the formation of the nicotinamide ring of NAD, the pyridine ring of pyridoxal, the pterin system of molybdopterin, and the thiazole and pyrimidine rings of thiamin are unknown. The sulfur transfer chemistry involved in the biosynthesis of lipoic acid, biotin, thiamin and molybdopterin is not yet understood. The formation of the isopentenylpyrophosphate precursor to the prenyl side chain of ubiquinone and menaquinone does not occur by the mevalonate pathway. None of the enzymes involved in this alternative terpene biosynthetic pathway have been characterized. The aim of this review is to focus attention on these unsolved mechanistic problems. 

The biosynthesis of molybdopterin is outlined in Fig. 19. The initial step involves rearrangement of guanosine triphosphate to precursor Z. Sulfur transfer followed by metallation and guanylation gives the cofactor. 

Mechanistic studies on the formation of the molybdopterin cofactor are still at an early stage. Conversion of guanosine, presumably as the triphosphate, to precursor Z occurs with retention of C-8 [84]. A possible mechanism for this third type of cyclohydrolase, which is consistent with the labeling experiment, is outlined in Fig. 20. (The other two types of cyclohydrolase are cyclohydrolase 1 for folate biosynthesis and cyclohydrolase II for riboflavin biosynthesis. In both cases, C8 is removed as formate.)... 

The use of ThiS-like proteins in biosynthetic sulfide transfer reactions is an emerging motif in natural product biosynthesis. Sequence analysis indicates that ThiS-like sequences are widespread and such proteins have now been experimentally characterized in the cysteine,molybdopterin, and thioquinolobactin biosynthetic pathways. 

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