Thank you Compo 1.78 t Crease was in conform to its su tures of 000 lutions Acti
ID: 481139 • Letter: T
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Thank you Compo 1.78 t Crease was in conform to its su tures of 000 lutions Active C The crys cose an 0.1 10 100 2A). The acid resi Compound A (HM of unequ separate for phosp molecule in GK(A1 dentified the two d The fold GK(41-11) et al., 199 nase is a mainly in t is approxi bly the res 0 10 20 30 40 50 minal and Glucose (mM and 54.4% tively, the Figure 1. Synthetic Activator of Glucokinase exhibit a si (A) Chemical formula of compound A. N.Thiazol 2-yl-2-amino-4- true of hexe and the ef- Magnani et fect of compound A on glucokinase enzymatic activity at 0.5 mM naselindic glucose concentration. induces a d (B) Rate versus glucose concentration plot in the absence (solid form in the circle) and presence of compound A (solid square, 30 LM). The hexokinase data were fit to Hill equation. The graph shows actual data with hexoki (symbols) and the best-fit line. large and s glucose and crystal structures of human glucokinase in both its ac form. As sExplanation / Answer
Figure 1A
The curve shown in figure-1A is the sigmoidal saturation curve which is obtained from co-crystallization of the deletion mutants glucokinase GK(1-11) with glucose and compound A, a synthetic activator. It displays the effect of compound A on Glucokinase enzymatic activity at 0.5 mM glucose concentration. This sigmoidal saturation curve with its substrate is the characteristic properties for acting as glucose sensor. Compound A is a potential activator for deletion mutants and wild-type glucokinase.
Figure 1B
Regarding the determination the active conformation of glucokinase, the used synthetic activator, compound A which is a potential activator towards deletion mutants and wild-type glucokinase changes the shapes the characteristic glucose saturation curve from sigmoidal to a Michaelis-Menten hyperbolic curve. It also increases Vmax. Compound A with 30µM concentration decreases the Hill coefficient from 1.78 to 1.11, and S0.5 value for glucose from 8 mM to 0.6 mM. It also decreases Vmax upto 1.6-fold.
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