COASY conclusion
Bifunctional Coenzyme A Synthase is integral to the CoA synthesis pathway (Zhyvoloup et. al., 2002), with its two domains, Dephospho-CoA Kinase (DPCK) and pantetheine-phosphate adenylyltransferase (PPAT), mediating the last two phases of this process (Figure 1). Structural analysis of sequence (Figure 10) and structure conservation (Figure 11) combined with electrostatic surface potential measurements(Figure 6), motif pattern searches (Table 1) and Multiple Sequence Alignments (Figure 14)have provided evidence for the location of the ATP binding P-Loop on the DPCK domain. This site is functionally significant as it forms one of the initial activating sites for the last stage of the CoA pathway (Zhyvoloup et. al., 2002).
The binding site for ACO was also identified on the DPCK domain (EMBL EBI, 2005). Whilst not directly related to the CoA pathway, ACO has a similar structure to Dephospho-CoA (Figure 16), which is created by the PPAT domain as the second last step of the CoA synthesis pathway, and is the product which feeds into the DPCK domain to produce CoA (Figure 1). The finding of a binding cleft(Figure 13) that may link the two domains provides support for the theory of a tunneling effect (Daugherty et. al., 2002), in which Dephospho-CoA is immediately passed to the DPCK domain for processing. This may explain the lack of dephospho-CoA accumulation in cells where CoAsy is expressed(Figure 3).
Therefore, our research has yielded new insights regarding the DPCK domain of mouse CoAsy. Future studies upon the PPAT domain, which was not present on CoAsy chain A, would provide valuable information to investigate the interaction between the two domains, and to further determine the mechanism of action of this essential enzyme.
Abstract | Introduction | Results | Discussion | Conclusion | Method | References
