Fumarase 2: Difference between revisions

Fumarase has the ability to catalyze the hydration of fumarate to malate or the dehydration of malate to fumarate.  The mechanism of fumarase in the hydration and dehydration reaction pathways remains simple, only involving three steps.  In the dehydration reaction, fumarase deprotonates a carbon atom on malate to form a carbanion (Beechmans 1998).  This deprotonation results in an aci-carboxylate intermediate (Weaver 2005).  After the intermediate forms, the acidic proton from the initial step removes the hydroxide group from the aci-carboxylate intermediate to form fumarase which then detaches from the active site of fumarase, completing the reaction (Rose, Weaver, 2004).  In the active site, amino acid residues involved in binding the substrate are located on three subunits: Thr100, Ser139, Ser140, and Asn141 from the b-subunit, Thr187 and His188 on the d-subunit, and Lys324 and Asn326 of the c-subunit (Beechmans 198).  The B site is located in a π-helix turn between the active site and solvent, and it includes residues Arg126, Lys127, Val128, His129, Pro130, Asn131, and  Asp132 all on the b-subunit.  Two hydrogen bonds initiate the binding of Asn131 and Asp132 residues with S-malate (Rose, Weaver, 2004).