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Catalytic Site Atlas

CSA LITERATURE entry for 1fdy

E.C. nameN-acetylneuraminate lyase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 4.1.3.3
CSA Homologues of 1fdyThere are 54 Homologs
CSA Entries With UniProtID P0A6L4
CSA Entries With EC Number 4.1.3.3
PDBe Entry 1fdy
PDBSum Entry 1fdy
MACiE Entry 1fdy

Literature Report

IntroductionThe N-acetylneuraminate lyase (NAL) enzymes are a subfamily of the (beta/alpha)8 enzymes. They all share a common catalytic step but catalyse reactions in different biological pathways. The formation of a Schiff base between a strictly conserved lysine residue and the C2 carbon of the common keto-acid moiety of the substrate is a common feature of the group, with the NAL enzymes catalysing the aldol cleavage of N-acetylneuraminate to form N-acetylmannosine and pyruvate via the distinctive Schiff base intermediate.
MechansimThe initial step is thought to be ring opening of the substrate alpha anomer. The conserved Lys165 then acts as nucleophile to the carbonyl group with concomitant proton transfer from the Lys165 nitrogen to the alcohol group of the tetrahedral intermediate. A second proton transfer results in a cationic oxonium group. The attacking nitrogen lone pair then kicks out a water molecule forming the substrate-enzyme Schiff base intermediate. A tyrosine group mediates the proton abstraction from the hydroxyl at the 4 position by the carboxylate group, leading to the formation of an enamine. Protonation at the methylene carbon then converts the enamine into an imine. Subsequent ring closure of N-acetylmannosine is spontaneous. The collapse of the enzyme-substrate intermediate is brought about by a hydrolytic water molecule which leads to the liberation of Lys165 and pyruvate.
Reaction

Catalytic Sites for 1fdy

Literature References

Notes:
Lawrence MC
Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase.
J Mol Biol 1997 266 381-399
PubMed: 9047371
Barbosa JA
Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme.
J Mol Biol 2000 303 405-421
PubMed: 11031117
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