2o1c
Structure of the E. coli dihydroneopterin triphosphate pyrophosphohydrolase
Structural highlights
FunctionNUDB_ECOLI Catalyzes the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. Required for efficient folate biosynthesis. Can also hydrolyze nucleoside triphosphates with a preference for dATP.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNudix 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. Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis.,Gabelli SB, Bianchet MA, Xu W, Dunn CA, Niu ZD, Amzel LM, Bessman MJ Structure. 2007 Aug;15(8):1014-22. PMID:17698004[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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