Conclusion

Succinyl-CoA Synthetase

These three molecules have displayed the diverse nature in which ligase molecules go about there activity.  The topology of the molecules and their active sites were very different.  The mechanism in which the enzyme catalyzed the reactions was very different each enzyme as well.   Thermodynamic considerations were somewhat similar for the Threonyl-tRNA synthetase acetyl-CoA carboxylase but vastly different for the succinyl-CoA synthetase.  Even the cellular location and cellular processes in which these enzymes were involved with were different for each enzyme.

All three enzymes had different secondary structures for the whole enzyme.  Threonyl-tRNA synthetase had an a+b secondary structure, where as the acetyl-CoA carboxylase had a/b secondary structure, and the Succinyl-CoA synthetase had a mix of a+b and a/b secondary structure depending on the subunit.  These variances did not stop at the secondary structure, but continued through out the whole molecule.  The active sites all had very different mechanics in how they functioned.  The threonyl-tRNA synthetase had a key Zn ligand and Arg -520 that caused it to be very selective to only binding to the amino acid threonine.  Acetyl-CoA carboxylase had rather different make up.  It had a pocket of amino acids (His 209-Glu 211, His 236-Glu 241, Glu 276, Ile 287-Glu 296, and Arg 338) that all seemed to function together in the amino acid to allow the active site to function as it should.  It also had a coenzyme (coenzyme A) that activated the protein.  The succinyl-CoA synthetase seemed to have many key elements that allowed the function of its active sites.  It had coenzyme A like acetyl-CoA carboxylase, but it also had the power helices that stabilized the phosphohistidine-246, and the multi-domains that were involve in the positioning of the GDP.

These three enzymes also displayed differences in the thermodynamics.  The threonyl-tRNA synthetase and acetyl-CoA carboxylase both required the consumption of ATP to ADP to allow this reaction to proceed spontaneously, but the succinyl-CoA synthetase actually produced a GTP.  It appears the citric acid reaction of succinyl-CoA to succinate is actually run in the opposite direction than that of the other two reactions studied.  These enzymes also all had different location in the cell, and were part of different cellular processes.  The threonyl-tRNA synthetase is found in the rough ER and is part of translation, the acetyl-CoA carboxylase is found in the cytosol and is part of fatty acid synthesis, and the succinyl-CoA synthetase is found in the mitochondria and is part of the citric acid cycle.  As you can see even though these three enzymes are part of the same class of enzymes they still have many differences.  This paper has truly shown my the diversity of the molecular world.

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