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Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis.
- Source :
-
Structure (London, England : 1993) [Structure] 2007 Aug; Vol. 15 (8), pp. 1014-22. - Publication Year :
- 2007
-
Abstract
- Nudix hydrolases are a superfamily of pyrophosphatases, most of which are involved in clearing the cell of potentially deleterious metabolites and in preventing the accumulation of metabolic intermediates. We determined that the product of the orf17 gene of Escherichia coli, a Nudix NTP hydrolase, catalyzes the hydrolytic release of pyrophosphate from dihydroneopterin triphosphate, the committed step of folate synthesis in bacteria. That this dihydroneopterin hydrolase (DHNTPase) is indeed a key enzyme in the folate pathway was confirmed in vivo: knockout of this gene in E. coli leads to a marked reduction in folate synthesis that is completely restored by a plasmid carrying the gene. We also determined the crystal structure of this enzyme using data to 1.8 A resolution and studied the kinetics of the reaction. These results provide insight into the structural bases for catalysis and substrate specificity in this enzyme and allow the definition of the dihydroneopterin triphosphate pyrophosphatase family of Nudix enzymes.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
Binding Sites
Catalysis
Conserved Sequence
Deoxyadenine Nucleotides metabolism
Escherichia coli genetics
Folic Acid analysis
Genes, Bacterial
Hydrogen Bonding
Hydrolysis
Kinetics
Models, Chemical
Models, Molecular
Molecular Sequence Data
Mutation
Neopterin analogs & derivatives
Neopterin biosynthesis
Neopterin metabolism
Open Reading Frames
Plasmids
Protein Binding
Protein Conformation
Protein Structure, Secondary
Pyrophosphatases genetics
Sequence Homology, Amino Acid
Substrate Specificity
X-Ray Diffraction
Nudix Hydrolases
Escherichia coli enzymology
Folic Acid biosynthesis
Pyrophosphatases chemistry
Pyrophosphatases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0969-2126
- Volume :
- 15
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Structure (London, England : 1993)
- Publication Type :
- Academic Journal
- Accession number :
- 17698004
- Full Text :
- https://doi.org/10.1016/j.str.2007.06.018