CoA Ligases

In its typical biochemical role, Coenzyme A (CoA) is covalently linked to metabolic intermediates through a high-energy bond (ΔGO°’ = -31.5 kJ/mol) between the pantetheine moiety of CoA and a carboxyl group. The thioester bond may be formed using the free energy of a metabolic reaction, as in the production of acetyl-CoA by pyruvate dehydrogenase or by the 3-ketoacyl thiolase reaction in the final step of each b-oxidation cycle. However, many carboxylate compounds are activated to the corresponding CoA derivative by the action of CoA ligase enzymes. The CoA ligase reaction proceeds through a two-step mechanism involving the conversion of the carboxylate and ATP to an enzyme-bound carboxyl-AMP intermediate with the release of PPi. Then, the activated carbonyl carbon of the adenylate is coupled to the thiol of CoA before AMP and the thioester are released from the enzyme. Hydrolysis of PPi in vivo makes the reaction irreversible:

CoA + R-COO- + ATP –> R-COSCoA + AMP + PPi

Closely related acyl carrier protein (ACP) ligases act in the same way since ACP shares the same phosphopantetheine prosthetic group, and a few CoA ligases are capable of using ACP as an alternative substrate. It is possible that a small number of the genes we are studying encode carboxy-ACP ligases. Also, one subset of the Arabidopsis AMP-binding proteins contains enzymes that activate carboxyl groups for conjugation to amino acids. The genes encoding these functions will not be studied under this grant. More broadly, the CoA ligases are related to firefly luciferase and to activation domains of proteins involved in non-ribosomal peptide synthesis. Crystal structures for luciferases and the PheA domain of gramicidin S synthetase are available, and these have been used as the basis for modeling the structures of several plant AAEs.

 

MIPS
At1g20480
At1g20490
At1g20500
At1g20510
At1g20560
At1g21530
At1g21540
At1g30520
At1g49430
At1g51680
At1g55320
At1g62940
At1g64400
At1g65060
At1g65880
At1g65890
At1g66120
At1g68270
At1g75960
At1g76290
At1g77240
At1g77590
At2g04350
At2g17650
At2g47240
At3g05970
At3g16170
At3g16910
At3g21230
At3g21240
At3g23790
At3g48990
At4g11030
At4g14070
At4g19010
At4g23850
At4g05160
At5g16340
At5g16370
At5g23050
At5g27600
At5g36880
At5g38120
At5g63380