The Rickettsia prowazekii Invasion Gene Homolog (invA) Encodes a Nudix Hydrolase Active on Adenosine (5′)-pentaphospho-(5′)-adenosine

Abstract

The genomic sequence of Rickettsia prowazekii, the obligate intracellular bacterium responsible for epidemic typhus, reveals an uncharacterized invasion gene homolog (invA). The deduced protein of 18,752 Da contains a Nudix signature, the specific motif found in the Nudix hydrolase family. To characterize the function of InvA, the gene was cloned and overexpressed in Escherichia coli. The expressed protein was purified to near homogeneity and subsequently tested for its enzymatic activity against a series of nucleoside diphosphate derivatives. The purified InvA exhibits hydrolytic activity toward dinucleoside oligophosphates (Np n N; n > 5), a group of cellular signaling molecules. At optimal pH 8.5, the enzyme actively degrades adenosine (

Complete Genome Sequence ofRickettsia typhiand Comparison with Sequences of Other Rickettsiae

“…Another protein implicated in the virulence of R. prowazekii is the dinucleoside polyphosphate hydrodolase, InvA. This protein is thought to function by hydrolyzing toxic dinucleoside oligophosphates within the host cell to produce ATP, thus providing an environment more conducive to growth (30,31). ORF RT0228 is 98% identical to the R. prowazekii InvA.…”

The NudA Protein in the Gastric Pathogen Helicobacter pylori Is an Ubiquitous and Constitutively Expressed Dinucleoside Polyphosphate Hydrolase

“…Although enzyme activities of Nudix proteins have been studied extensively, the biological role of these enzymes is still poorly understood (3)(4)(5)(6). It has been proposed that Nudix hydrolases are housecleaning enzymes that decrease the intracellular level of toxic substances and cell signaling molecules, e.g.…”

Structure of a Coenzyme A Pyrophosphatase from Deinococcus radiodurans : a Member of the Nudix Family

“…A large number of sequences containing the Nudix motif have been found in the genomes of species from all three kingdoms, in organisms ranging in complexity from viruses to humans. Many of these proteins have been enzymatically characterized; their substrates include nucleoside triphosphates (5,8,27,28), coenzymes (2,14,17,29,39), sugar nucleotides (25,39,40), and dinucleoside polyphosphates (1,9,10,18,29,33). These substrates are either potentially toxic compounds, cell signaling molecules, regulators of cellular metabolism, or metabolic intermediates whose concentrations require modulation in different stages of the cell cycle.…”