Prostaglandin H2 (PGH2) 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 PGH2 has been reported. Hence, understanding the interactions of PGH2 and characterizing its binding sites in these synthases is crucial for developing novel therapeutics based on these proteins as targets.