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From Proteopedia

is a vital part of the citric acid cycle. It aids in the reversible hydration and dehydration of malate to fumarate and overall in the production of NADH. Genetic mutations of fumarase has often been associated with the development of leiofibromyomas in the skin and uterus in combination with renal cancer. Studies have been conducted to explore the possible connections present with a heritable cancer predispositions for young females with a history of uterine fibroids, related to Reed Syndrome. Neurological abnormalities can result from a fumarase deficiency a problem with the synthesis of the enzyme. A mutation of the enzyme fumarase can result in a build-up of fumarate, ultimately interrupting the normal processes of metabolism.

Fumarase

This image depicts the of fumarase(1FUO). Alpha helices are represented in coral color, and beta sheets are yellow. Alpha helices make up most of the structure of fumarase. There are also random chains colored blue and green within this depiction of its secondary structure. The ligand is represented by red and gray molecules at the end of the alpha helices. The of fumarase allow for the coiled coil of the alpha helices to exist.

Some of the portions of fumarase (gray) and portions (red) illustrate the complex interactions between residues. It can also be observed that many hydrophobic portions are present within the tertiary structure of coiled coils. is shown through the blue spheres representing water molecules (the solvent) and the ribbon structure of fumarase (white). The ligand is represented in orange. As can be seen, the center of the coiled coil is inaccessible to solvent, as is center of the protein, where the catalytic residues are present. There are two active sites on fumarase, where the (wire and stick representation) bind to the molecule. As can be seen in the model, the side chains that interact with the ligands possess a positive charge, creating covalent bonds with the ligands which contain several carbonyl carbons. Malate, Citrate and water are the ligands present at the end of the alpha helices.

In fumarase, are illustrated in a green, wire and stick representations. are represented in purple wire and stick representations.

Fumarase is often seen in tetramer forms, interlocking four fumarases in such a way that the catalytic residues within the center of the protein and the residues in close proximity to the ligand are able to interact with the other tertiary structures in the tetramer to have the enzymatic function as desired.