Allosteric Regulation of Human Ribokinase: Structural Insights into Na+ and K+-mediated Catalysis

Monday, March 2, 1-2 p.m.

CSF-1302

Hello Everyone,

You are warmly invited to attend the upcoming seminar on Monday, March 2^nd, 2026. Please find the details below.

March 2^nd, 2026

1:00 p.m. – 2:00 p.m.

CSF-1302

The direct link for the meeting is:

https://mun.webex.com/mun/j.php?MTID=mfb53992e04b0b2aa7d61cfc9b927a16e

Speaker: Naomi Akanmori (Park lab, PhD Student, Biochemistry)

Title: Allosteric regulation of human ribokinase (RK): structural insights into Na+ and K+-mediated catalysis

Abstract:

Ribose is an essential precursor for nucleotides, amino acids, enzyme cofactors, and cellular energy metabolism. The first step in its metabolism is an ATP-dependent phosphorylation to ribose-5-phosphate by ribokinase (RK), a conserved enzymean enzyme conserved across all domains of life. This step produces ribose-5-phosphate, which subsequently enters central metabolic pathways such as the pentose phosphate pathway and glycolysis. Human RK exhibits a distinct dependence on monovalent cations (M+), demonstrating significantly higher catalytic an activation effect on activity in the presence of larger cations such as K⁺ and no effect in the presence of smaller cation Na⁺. In the absence of monovalent cations, the ATP-binding region is disordered, resulting in an inactive RKenzyme. The structural basis for this ion selectivity and its allosteric effect on ATP binding hydrolysis remains unclear. We hypothesize that monovalent cation binding induces conformational changes in RK that influence ATP binding. To test this, we performed crystallographic analysis of human RK in multiple ligand-bound states with K⁺ and Na⁺. To date, we have resolved eleven crystal structures, including nine Na⁺-bound and three newly released K⁺-bound forms spanning distinct stages of the catalytic cycle. We observed a unique conformational change induced by K+ binding at the allosteric M+ binding site: a peptide plane flip between Gly306 and Thr307, with unknown functional significancerelevance. Interestingly, Na⁺-bound structures reveal a pronounced flexibility within the triphosphate moiety of ATP. In contrast, K⁺-bound structures position the γ-phosphate of ATP within a catalytically favourable distance of <5 Å to ribose. A nearby Mg2+ ion may stabilize the ATP triphosphate, but its specific role remains to be clarified, as prior Na+-bound structures lacked Mg2+. Complementary molecular dynamics simulations revea l a stabilizing effect on the B-factors of ATP-binding site residues when K+ is bound. and B-factor analyses corroborate these ion-dependent differences in ATP binding loop stabilization. Together, these findings support a model where K+ binding promotes correct ATP alignment and may trigger structural changes required for activation. Upcoming work is aimed at dissecting the distinct contributions of K⁺ and Mg²⁺ to the catalytically competent conformation of ATP.

All are welcome to attend. Please mark your calendars and join us for this exciting presentation.

Best regards,

Presented by Department of Human Biosciences

Event Listing 2026-03-02 13:00:00 2026-03-02 14:00:00 America/St_Johns Allosteric Regulation of Human Ribokinase: Structural Insights into Na+ and K+-mediated Catalysis Hello Everyone, You are warmly invited to attend the upcoming seminar on Monday, March 2nd, 2026. Please find the details below. March 2nd, 2026 1:00 p.m. – 2:00 p.m. CSF-1302 The direct link for the meeting is: https://mun.webex.com/mun/j.php?MTID=mfb53992e04b0b2aa7d61cfc9b927a16e Speaker: Naomi Akanmori (Park lab, PhD Student, Biochemistry) Title: Allosteric regulation of human ribokinase (RK): structural insights into Na+ and K+-mediated catalysis Abstract: Ribose is an essential precursor for nucleotides, amino acids, enzyme cofactors, and cellular energy metabolism. The first step in its metabolism is an ATP-dependent phosphorylation to ribose-5-phosphate by ribokinase (RK), a conserved enzymean enzyme conserved across all domains of life. This step produces ribose-5-phosphate, which subsequently enters central metabolic pathways such as the pentose phosphate pathway and glycolysis. Human RK exhibits a distinct dependence on monovalent cations (M+), demonstrating significantly higher catalytic an activation effect on activity in the presence of larger cations such as K⁺ and no effect in the presence of smaller cation Na⁺. In the absence of monovalent cations, the ATP-binding region is disordered, resulting in an inactive RKenzyme. The structural basis for this ion selectivity and its allosteric effect on ATP binding hydrolysis remains unclear. We hypothesize that monovalent cation binding induces conformational changes in RK that influence ATP binding. To test this, we performed crystallographic analysis of human RK in multiple ligand-bound states with K⁺ and Na⁺. To date, we have resolved eleven crystal structures, including nine Na⁺-bound and three newly released K⁺-bound forms spanning distinct stages of the catalytic cycle. We observed a unique conformational change induced by K+ binding at the allosteric M+ binding site: a peptide plane flip between Gly306 and Thr307, with unknown functional significancerelevance. Interestingly, Na⁺-bound structures reveal a pronounced flexibility within the triphosphate moiety of ATP. In contrast, K⁺-bound structures position the γ-phosphate of ATP within a catalytically favourable distance of <5 Å to ribose. A nearby Mg2+ ion may stabilize the ATP triphosphate, but its specific role remains to be clarified, as prior Na+-bound structures lacked Mg2+. Complementary molecular dynamics simulations revea l a stabilizing effect on the B-factors of ATP-binding site residues when K+ is bound. and B-factor analyses corroborate these ion-dependent differences in ATP binding loop stabilization. Together, these findings support a model where K+ binding promotes correct ATP alignment and may trigger structural changes required for activation. Upcoming work is aimed at dissecting the distinct contributions of K⁺ and Mg²⁺ to the catalytically competent conformation of ATP. All are welcome to attend. Please mark your calendars and join us for this exciting presentation. Best regards, CSF-1302 Department of Human Biosciences