%0 Journal Article %J Acta Crystallogr F Struct Biol Commun %D 2018 %T Crystal structures and kinetics of N-acetylneuraminate lyase from Fusobacterium nucleatum. %A Kumar, Jay Prakash %A Rao, Harshvardhan %A Nayak, Vinod %A Ramaswamy, S %K Bacterial Proteins %K Crystallography, X-Ray %K Fusobacterium nucleatum %K Hydrogen Bonding %K Models, Molecular %K N-Acetylneuraminic Acid %K Oxo-Acid-Lyases %K Protein Conformation %K Protein Folding %K Pyruvic Acid %K Schiff Bases %K Sequence Alignment %K Tyrosine %X

N-Acetyl-D-neuraminic acid lyase (NanA) catalyzes the breakdown of sialic acid (Neu5Ac) to N-acetyl-D-mannosamine (ManNAc) and pyruvate. NanA plays a key role in Neu5Ac catabolism in many pathogenic and bacterial commensals where sialic acid is available as a carbon and nitrogen source. Several pathogens or commensals decorate their surfaces with sialic acids as a strategy to escape host innate immunity. Catabolism of sialic acid is key to a range of host-pathogen interactions. In this study, atomic resolution structures of NanA from Fusobacterium nucleatum (FnNanA) in ligand-free and ligand-bound forms are reported at 2.32 and 1.76 Å resolution, respectively. F. nucleatum is a Gram-negative pathogen that causes gingival and periodontal diseases in human hosts. Like other bacterial N-acetylneuraminate lyases, FnNanA also shares the triosephosphate isomerase (TIM)-barrel fold. As observed in other homologous enzymes, FnNanA forms a tetramer. In order to characterize the structure-function relationship, the steady-state kinetic parameters of the enzyme are also reported.

%B Acta Crystallogr F Struct Biol Commun %V 74 %P 725-732 %8 2018 Nov 01 %G eng %N Pt 11 %R 10.1107/S2053230X18012992 %0 Journal Article %J Acta Crystallogr F Struct Biol Commun %D 2017 %T Crystal structure of N-acetylmannosamine kinase from Fusobacterium nucleatum. %A Caing-Carlsson, Rhawnie %A Goyal, Parveen %A Sharma, Amit %A Ghosh, Swagatha %A Setty, Thanuja Gangi %A North, Rachel A %A Friemann, Rosmarie %A Ramaswamy, S %K Adenosine Triphosphate %K Amino Acid Sequence %K Bacterial Proteins %K Binding Sites %K Cloning, Molecular %K Crystallography, X-Ray %K Escherichia coli %K Fusobacterium nucleatum %K Gene Expression %K Genetic Vectors %K Hexosamines %K Models, Molecular %K Phosphotransferases (Alcohol Group Acceptor) %K Protein Binding %K Protein Conformation, alpha-Helical %K Protein Conformation, beta-Strand %K Protein Interaction Domains and Motifs %K Protein Multimerization %K Recombinant Proteins %K Sequence Alignment %K Sequence Homology, Amino Acid %K Substrate Specificity %X

Sialic acids comprise a varied group of nine-carbon amino sugars that are widely distributed among mammals and higher metazoans. Some human commensals and bacterial pathogens can scavenge sialic acids from their environment and degrade them for use as a carbon and nitrogen source. The enzyme N-acetylmannosamine kinase (NanK; EC 2.7.1.60) belongs to the transcriptional repressors, uncharacterized open reading frames and sugar kinases (ROK) superfamily. NanK catalyzes the second step of the sialic acid catabolic pathway, transferring a phosphate group from adenosine 5'-triphosphate to the C6 position of N-acetylmannosamine to generate N-acetylmannosamine 6-phosphate. The structure of NanK from Fusobacterium nucleatum was determined to 2.23 Å resolution by X-ray crystallography. Unlike other NanK enzymes and ROK family members, F. nucleatum NanK does not have a conserved zinc-binding site. In spite of the absence of the zinc-binding site, all of the major structural features of enzymatic activity are conserved.

%B Acta Crystallogr F Struct Biol Commun %V 73 %P 356-362 %8 2017 Jun 01 %G eng %N Pt 6 %R 10.1107/S2053230X17007439