MgATP coordination isomers

AMP = adenosine monophosphate Figure 12 Coordination isomers of MgATP... 

Only one coordination isomer is likely to be the true substrate in the active site of an enzyme. The reason for expecting this to be so is that it is almost certain that only one transition state is involved in a given step of an enzymic reaction, and the structure of this transition state will be strongly influenced by enzymic binding interactions. These binding interactions will manifest themselves in the ground states of complexes such as E-MgATP. They will tend to... 

The substrate for many phosphotransferases is MgATP. Which of the possible isomers of this chelate complex is utilized by these enzymes Since Mg2+ associates and dissociates rapidly from the complexes there are several possibilities a tridentate complex with oxygens from a, (3, and y phospho groups coordinated with the metal ion, an a,(3-bidentate, a (3,y-bidentate, or a monodentate complex. Most evidence suggests that P,y-bidentate complexes of the following types are the true substrates. 

The glucose-6-P remains in the coordination sphere of the cobalt. Only one-half of the mixture of the two isomers was a substrate the part remaining was inert, although it did inhibit. The inert material and the product were separated and a degradation product of the inert material was crystallized. The absolute stereochemistry was determined by x-ray crystallography (44). The active isomer of Co(NH3)4ATP used by hexokinase was found to correspond to the A isomer of /i,y-bidentate MgATP (43). 

The isomer designated as A is the one that, when viewed from the side of the ring from whieh AMP is projected, shows the closest pathway from Mg to AMP in clockwise rotation. The isomer is designated as A when the shortest path from Mg to AMP is in the counterclockwise direction. The two isomers shown are the /J.y-bidentate isomers. There are 15 other possible monodentate, bidentate, and tridentate isomers of MgATP, all of which are in rapid coordination exchange equilibrium with one another in aqueous solution. 

Coordination exchange-inert metal nucleotide complexes have been synthesized, their structural and stereoisomers have been separated by chromatographic and enzymic methods, and their structures have been determined by X-ray crystallography and correlated to their circular dichroism and P NMR spectra. The pure isomers have been tested as substrates for enzymes in place of MgATP or MgADP, and from the results the structures of the enzyme-bound and active isomers have been deduced. The most widely used complexes of this type have been Cr(III)-aquo complexes and Co(III)-ammine complexes such as those shown below. 

MgATP exists as a rapidly equilibrating complex [dissociating 7000 times per second (22)], with full coordination to the /3- and y-phosphates and approximately 50% coordination at the a-phosphate. The bidentate isomers can exist as two screw-sense isomers ... 

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