Abstract
Inorganic polyphosphate (poly(P)) is a biological high energy compound presumed to be an ancient energy carrier preceding ATP. Several poly(P)-dependent kinases that use poly(P) as a phosphoryl donor are known to function in bacteria, but crystal structures of these kinases have not been solved. Here we present the crystal structure of bacterial poly(P)/ATP-glucomannokinase, belonging to Gram-positive bacterial glucokinase, complexed with 1 glucose molecule and 2 phosphate molecules at 1.8 A resolution, being the first among poly(P)-dependent kinases and bacterial glucokinases. The poly(P)/ATP-glucomannokinase structure enabled us to understand the structural relationship of bacterial glucokinase to eucaryotic hexokinase and ADP-glucokinase, which has remained a matter of debate. These comparisons also enabled us to propose putative binding sites for phosphoryl groups for ATP and especially for poly(P) and to obtain insights into the evolution of kinase, particularly from primordial poly(P)-specific to ubiquitous ATP-specific proteins.
Highlights
Inorganic polyphosphate (poly(P)) is a biological high energy compound presumed to be an ancient energy carrier preceding ATP
The poly(P)/ATP-glucomannokinase structure enabled us to understand the structural relationship of bacterial glucokinase to eucaryotic hexokinase and ADP-glucokinase, which has remained a matter of debate
Crystal structures of eucaryotic HKs from yeast (9 –13), human (14 –19), rat (20), and parasite Schistosoma mansoni (20) have been solved, no crystal structure has been reported for Grampositive or negative bacterial GKs
Summary
The poly(P)/ATP-glucomannokinase structure enabled us to understand the structural relationship of bacterial glucokinase to eucaryotic hexokinase and ADP-glucokinase, which has remained a matter of debate. Poly(P)-dependent kinases have ATP-specific partners, and a knowledge of the crystal structure of poly(P)-dependent kinase may aid in understanding the structural relationship of poly(P)-dependent kinase to the ubiquitous ATP-specific kinase, i.e. to understand structural determinants enabling poly(P)/ATP-type and poly(P)-specific type kinases to use poly(P), ATP-specific kinase to reject poly(P) and poly(P)-specific kinase to reject ATP Such understanding would lend insights into the evolutionary relationship of poly(P)-dependent kinase to ubiquitous ATP-specific kinase, where relationships are of interest, since poly(P) could be formed and participate in ATP synthesis under ancient prebiotic conditions and serve as a possible ancient energy carrier preceding ATP (5). We show the crystal structure of GMK complexed with one glucose and two phosphate (PO42Ϫ) molecules, the first among poly(P)-dependent kinases and bacterial GKs. Crystal structural analysis for GMK provides evidence for close crystal structural and evolutionary relationships between bacterial.
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