Sandbox Wabash 11 Fumarase

Kyle Stucker

Fumarase C

Found in E. Coli, Fumarase C is an enzyme that catalyzes L-malate and fumarate. It belongs to a family of enzymes that includes aspartase, arginosuccinate lyase, adenlosuccinate lyase, and gamma-crysatallin. It is tetrameric and has approximately 460 amino acids in each monomer. (Weaver et. al. 834).

The Debate About Two Possible Locations of the Active Site

Many studies of Fumarase have shown that there are two different binding sites for carboxylic acid. One of the two sites (Site A), is formed by the residues from three subunits and is located at the tungstate sight. The active site is very deep and contains His-188, Ser-98, Thr-100, Asn-141. Site A also utilizes hydrogen bonding between a water molecule and His-188 to increase stability of substrate. The second site (Site B), is formed from atoms in a single subunit and contains L-malate. Site B is close to the surface of the enzymes and is composed of Asn-131, Asp-132, His-129, and Arg-126. A study conducted by Todd Weaver, Mason Lees, and Leonard Banaszak confirmed that Site A was the actual active site by mutating the at Site B into Arginine and observing which mutation most effected substrate binding. The mutated was the mutation that affected activity the most. The un-mutated form of Fumarase had an activity of 4920.0 microunits/mL. When His-188 was mutated the activity of the enzyme was only at microunits/mL, but the His-129 mutation still allowed for 2080.0 microunits/mL. These results showed that Site A was the active site.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Function

Disease

Relevance

Structural highlights

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