RT Journal Article
T1 Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases
A1 Nagy, Gergely
A1 Suardíaz Delrío, Reynier
A1 Lopata, Anna
A1 Ozohanics, Olivér
A1 Vékey, Károly
A1 Brooks, Bernard
A1 Leveles, Ibolya
A1 Tóth, Judit
A1 Vértessy, Beata
A1 Rosta, Edina
AB Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the γ-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases.
PB American Chemical Society
SN 0002-7863
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/92421
UL https://hdl.handle.net/20.500.14352/92421
LA eng
NO Nagy, Gergely N., et al. «Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases». Journal of the American Chemical Society, vol. 138, n.o 45, noviembre de 2016, pp. 15035-45. https://doi.org/10.1021/jacs.6b09012.
NO Engineering & Physical Sciences Research Council (Reino Unido)
NO European Commission
NO Biotechnology and Biological Sciences Research Council (Reino Unido)
NO Hungarian Scientific Research Fund
NO Hungarian Academy of Sciences
DS Docta Complutense
RD 5 abr 2025