| http://purl.uniprot.org/citations/24152047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24152047 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24152047 | http://www.w3.org/2000/01/rdf-schema#comment | "N-Acetylneuraminate lyases (NALs) or sialic acid aldolases catalyze the reversible aldol cleavage of N-acetylneuraminic acid (Neu5Ac, the most common form of sialic acid) to form pyruvate and N-acetyl-d-mannosamine. Although equilibrium favors sialic acid cleavage, these enzymes can be used for high-yield chemoenzymatic synthesis of structurally diverse sialic acids in the presence of excess pyruvate. Engineering these enzymes to synthesize structurally modified natural sialic acids and their non-natural derivatives holds promise in creating novel therapeutic agents. Atomic-resolution structures of these enzymes will greatly assist in guiding mutagenic and modeling studies to engineer enzymes with altered substrate specificity. We report here the crystal structures of wild-type Pasteurella multocida N-acetylneuraminate lyase and its K164A mutant. Like other bacterial lyases, it assembles into a homotetramer with each monomer folding into a classic (β/α)₈ TIM barrel. Two wild-type structures were determined, in the absence of substrates, and trapped in a Schiff base intermediate between Lys164 and pyruvate, respectively. Three structures of the K164A variant were determined: one in the absence of substrates and two binary complexes with N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Both sialic acids bind to the active site in the open-chain ketone form of the monosaccharide. The structures reveal that every hydroxyl group of the linear sugars makes hydrogen bond interactions with the enzyme, and the residues that determine specificity were identified. Additionally, the structures provide some clues for explaining the natural discrimination of sialic acid substrates between the P. multocida and Escherichia coli NALs."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi4011754"xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi4011754"xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Cao H."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Cao H."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Fisher A.J."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Fisher A.J."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Yu H."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Yu H."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Tiwari V.K."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Tiwari V.K."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Aye A."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Aye A."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Huynh N."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Huynh N."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Shin D.W."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/author | "Shin D.W."xsd:string |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24152047 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |