Deciphering the catalytic machinery in a universally conserved ribosome binding ATPase YchF

A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli

“…Because of its structural characteristics, YchF was proposed to bind to ribosomes as well as to nucleic acids (4) and was classified as a member of the translation factor family of nucleotide-hydrolyzing proteins (TRAFAC family). Consistent with this idea, YchF was shown to bind to ribosomes in the protozoan parasite Trypanosoma cruzi and in the proteobacterium E. coli (3,5). Additionally, the yeast homologue of YchF, Ybr025c, was suggested to interact with the elongation factor eEF1 (6).…”

“…YchF differs from the other GTPases because it preferentially hydrolyzes ATP over GTP (2), thereby functioning as an ATPase. This altered nucleotide specificity is due to the replacement of a conserved lysine residue within the nucleotide binding motif by valine in the Escherichia coli YchF or by leucine in the human YchF homologue hOla1 3 (2,3). Although the x-ray structures of YchF from Haemophilus influenzae and human Ola1 have been determined (2,4), the exact function of these ATPases is unknown.…”

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

“…Many Obg-like G/ ATPases are involved in ribosome biogenesis and ribosome binding has been observed for Escherichia coli (6,49) and Trypanosoma cruzi (16) YchF. The exact impact of YchF on ribosome biogenesis or translation is unknown, but yeast Ola1 possibly influences translational fidelity (39).…”

“…At least 20 GTPase families have been identified based on structural features and eight of these families are universally conserved in eukaryotes, bacteria, and archaea. Within the Obg (spo0B-associated GTP-binding protein) family of GTPases, the YchF/Ola1 proteins constitute an unconventional subfamily because they hydrolyze ATP rather than GTP (24,49). This is due to an altered G4 motif in the nucleotide-binding domain,…”

Histidine 114 Is Critical for ATP Hydrolysis by the Universally Conserved ATPase YchF

“…Unfortunately, these x-ray crystallography structures do not provide structural information for critical regions of the protein, including both switch regions and a flexible loop located in the G-domain. Furthermore, mutational analyses have revealed that two residues, Asn-13 and Lys-78 (E. colinumbering),playimportantrolesinthepotassiumdependence of ATP hydrolysis, but amino acid residues essential for ATP hydrolysis have yet to be identified (12). Thus, the current structural and biochemical information on YchF is insufficient to devise a reliable mechanism for ATP hydrolysis by YchF.…”