An ATPase with a twist: A unique mechanism underlies the activity of the bacterial tyrosine kinase, Wzc.
Sci Adv
; 7(39): eabj5836, 2021 Sep 24.
Article
in En
| MEDLINE
| ID: mdl-34550748
ABSTRACT
BY-kinases constitute a protein tyrosine kinase family that encodes unique catalytic domains that deviate from those of eukaryotic kinases resembling P-loop nucleotide triphosphatases (NTPases) instead. We have used computational and supporting biochemical approaches using the catalytic domain of the Escherichia coli BY-kinase, Wzc, to illustrate mechanistic divergences between BY-kinases and NTPases despite their deployment of similar catalytic motifs. In NTPases, the "arginine finger" drives the reactive conformation of ATP while also displacing its solvation shell, thereby making favorable enthalpic and entropic contributions toward ßγ-bond cleavage. In BY-kinases, the reactive state of ATP is enabled by ATP·Mg2+-induced global conformational transitions coupled to the conformation of the Walker-A lysine. While the BY-kinase arginine finger does promote the desolvation of ATP, it does so indirectly by generating an ordered active site in combination with other structural elements. Bacteria, using these mechanistic variations, have thus repurposed an ancient fold to phosphorylate on tyrosine.
Full text:
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Sci Adv
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos