title: Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase.
abstract: We describe here a sub-family of enzymes related both structurally and functionally to N-acetylneuraminate lyase. Two members of this family (N-acetylneuraminate lyase and dihydrodipicolinate synthase) have known three-dimensional structures and we now proceed to show their structural and functional relationship to two further proteins, trans-o-hydroxybenzylidenepyruvate hydratase-aldolase and D-4-deoxy-5-oxoglucarate dehydratase. These enzymes are all thought to involve intermediate Schiff-base formation with their respective substrates. In order to understand the nature of this intermediate, we have determined the three-dimensional structure of N-acetylneuraminate lyase in complex with hydroxypyruvate (a product analogue) and in complex with one of its products (pyruvate). From these structures we deduce the presence of a closely similar Schiff-base forming motif in all members of the N-acetylneuraminate lyase sub-family. A fifth protein, MosA, is also confirmed to be a member of the sub-family although the involvement of an intermediate Schiff-base in its proposed reaction is unclear.
authors.affiliation: Biomolecular Research Institute, Parkville, Victoria, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Lawrence
authors.forename: J A
authors.initials: JA
authors.lastname: Barbosa
authors.forename: B J
authors.initials: BJ
authors.lastname: Smith
authors.forename: N E
authors.initials: NE
authors.lastname: Hall
authors.forename: P A
authors.initials: PA
authors.lastname: Pilling
authors.forename: H C
authors.initials: HC
authors.lastname: Ooi
authors.forename: S M
authors.initials: SM
authors.lastname: Marcuccio
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001894:Borohydrides / Q000737:chemistry; D019755:Carbon-Carbon Lyases; D003016:Clostridium perfringens / Q000187:drug effects / Q000201:enzymology; D017124:Conserved Sequence; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011773:Pyruvates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D001894:Borohydrides; D004791:Enzyme Inhibitors; D011773:Pyruvates; C012375:hydroxypyruvic acid; C104866:MosA protein, Rhizobium meliloti; D019755:Carbon-Carbon Lyases; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase