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Catalytic Site Atlas

CSA LITERATURE entry for 1fuq

E.C. namefumarate hydratase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1fuqThere are 46 Homologs
CSA Entries With UniProtID P05042
CSA Entries With EC Number
PDBe Entry 1fuq
PDBSum Entry 1fuq
MACiE Entry 1fuq

Literature Report

IntroductionFumarase catalyses the reversible stereospecific hydration/dehydration of fumarate to L-malate during Kreb's cycle. Fumarase C is a member of the class II enzymes, a family which also includes aspartase, adenylosuccinate lyase and arginosuccinate, with high sequence similarity among its members. Fumarse C differs from the class I fumarase A and B enzymes in its lack of an apparent iron sulphur cluster.
MechansimThe catalytic site is formed from residues which span three of the four enzyme subunits.
In the direction of fumarate formation, a catalytic base, His188 (A) first activates a water molecule towards abstracting the C3 proton of the malate substrate. This generates an unstable carbanion which rearranges to the aci-carboxylate intermediate with concomitant proton donation to the enzyme, leaving the enzyme in a doubly protonated state. The catalytic K324 (B)then acts as a general acid to a departing OH group from the C2 position, resulting in the loss of water and the formation of fumarate. The 'sticky' proton left on the enzyme is displaced by the binding of another malate molecule.

Catalytic Sites for 1fuq

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA188188macie:sideChainThe residue is catalytically important to the first step of the reaction, activating a water molecule to act as a base towards the C3 proton of malate. The residue its self is activated towards this role through an electrostatic interaction with Glu331, a connection which later in the reaction facilitates a proton relay from the enzyme to the solvent.
GluB331331macie:sideChainThe residue is thought to activate His188 towards catalysis by modifying its pKa through electrostatic interactions. This interaction then forms the pathway for proton relay from the enzyme to the solvent when a second malate substrate molecule binds in the active site.
LysB324324macie:sideChainThe residue acts as a general acid towards the departing OH group from C2 of the aci-carboxylate intermediate. The residue's positively charged side chain is also thought to stabilise the resulting carbanion from the initiated reaction step, and therefore facilitate the formation of the intermediate.

Literature References

Weaver T
Crystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli.
Biochemistry 1996 35 13955-13965
PubMed: 8909293