A-ATP Synthase

In "'F-ATP Synthase"' the homolog to S238 is the non polar A158. Since A158 cannot form hydrogen bonds to interact with the substrate, the P-loop undergoes a conformational change. In A-ATP Synthase the close proximity needed between S238 and the vandate during transition state is achieved with a hydrogen bond, not a conformational change in the P-loop.

L417 Is involved in a bifurcated hydrogen bond. K240 T241 interact with Mg+ [10]

R349-

Residues that stabilizes the arched P-loop include P235 ----F236*subunit beta in moving towards the y-phosphate of ATP during catalysis. also stabilized by weak non-polar interactions and polar. K162+ R189+ E188-

These increased proximities of the catalytically important residues clearly demonstrate that structural rearrangement occurs during catalysis in subunit A.

Significance of the Second Vandate

The second vandate is positioned in a region exactly opposite the nucleotide-binding site, where the ATP molecule transiently associates on its way to the final binding pocket in subunit "'B"'. [25] Similar binding behavior was observed for "'As"' [10] indicating that the substrate molecule has a similar path of entry to the active site in both the "'A"' and '"B"' subunit of the A-ATP synthase and that they have a transient binding position near the P-Loop. It is proposed that Pi binds first to the catalytic site and sterically hinders ATP binding, thereby selectively allowing binding of ADP [14] The "'Avi"' structure confirms this, since although both ADP and Vi were present in the crystallized solution, the catalytic A-subunit first permits only the binding of the phosphate analogue Vi. Hence the present "Avi"' structure represents a trapped initial transition state showing for the first time both the entering path and the final Vi-bound state in the catalytic subunit.

Conclusion

The active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme.[29] As a result, the substrate does not simply bind to a rigid active site; the amino acid side chains which make up the active site are molded into the precise positions that enable the enzyme to perform its catalytic function. Stabilization of the transition state supports the induced fit model. A-ATP synthase lowers the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate—by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition).

when the enzyme is complementary to the substrate, the E.S. complex is more stable, has less free energy in the ground state than substrate alone. You increase the activation energy.

Avi "loose state"-closes up around molecules and binds them loosely (transition state has more free energy than both S and P)

(P loop intermediate S238 closest G234 residue sidechain k240 P loop closer)

Adp(ADP bound) Apnp (AMP-PNP bound) "tight state"- forces molecules together, binding ATP with high affinity

(P loop closest S238 int K240 significant)

possible sources of error can be the fact that ADp is not bound during transition state? is synthase reversible? where is it located? absence of ADP, may not affect the formation of transition-like state because of example