Comparison of PGH(2 )binding site in prostaglandin synthases

BACKGROUND: Prostaglandin H(2 )(PGH(2)) is a common precursor for the synthesis of five different Prostanoids via specific Prostanoid Synthases. The binding of this substrate with these Synthases is not properly understood. Moreover, currently no crystal structure of complexes bound with PGH(2 )has been reported. Hence, understanding the interactions of PGH(2 )and characterizing its binding sites in these synthases is crucial for developing novel therapeutics based on these proteins as targets. RESULTS: Shape and physico-chemical properties of the PGH(2 )binding sites of the four prostanoid synthases were analyzed and compared in order to understand the molecular basis of the specificity. This study provides models with predicted pockets for the binding of PGH(2 )with PGD, PGE, PGF and PGI Synthases. The results closely match with available experimental data. The comparison showed seven physico-chemical features that are common to the four PGH(2 )binding sites. However this common pattern is not statistically unique and is not specific enough to distinguish between proteins that can or cannot bind PGH(2). A large scale search in ASTRAL data bank, a non redundant Protein Data Bank, for a similar pattern showed the uniqueness of each of the PGH(2 )binding site in these Synthases. CONCLUSION: The binding pockets in PGDS, PGES, PGFS and PGIS are unique and do not share significant commonality which can be characterized as a PGH(2 )binding site. Local comparison of these protein structures highlights a case of convergent evolution in analogous functional sites