title: Crystal structures of LacD from Staphylococcus aureus and LacD.1 from Streptococcus pyogenes: insights into substrate specificity and virulence gene regulation.
abstract: Staphylococcus aureus LacD, a Class I tagatose-1,6-bisphosphate (TBP) aldolase, shows broadened substrate specificity by catalyzing the cleavage of 1,6-bisphosphate derivatives of D-tagatose, D-fructose, D-sorbose, and D-psicose. LacD.1 and LacD.2 are two closely-related Class I TBP aldolases in Streptococcus pyogenes. Here we have determined the crystal structures of S. aureus LacD and S. pyogenes LacD.1. Monomers of both enzymes are folded into a (β/α)(8) barrel and two monomers associate tightly to form a dimer in the crystals. The structures suggest that the residues E189 and S300 of rabbit muscle Class I fructose-1,6-bisphosphate (FBP) aldolase are important for substrate specificity. When we mutated the corresponding residues of S. aureus LacD, the mutants (L165E, L275S, and L165E/L275S) showed enhanced substrate specificity toward FBP.
authors.affiliation: Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sang Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hyoun Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Do Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Kyoung Hoon
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Yoon
authors.forename: Se Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D020125:Mutation, Missense; D013211:Staphylococcus aureus / Q000201:enzymology*; D013297:Streptococcus pyogenes / Q000201:enzymology*; D013379:Substrate Specificity; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D000446:Aldehyde-Lyases; C023093:tagatose 1,6-diphosphate aldolase