title: X-ray structures of threonine aldolase complexes: structural basis of substrate recognition.
abstract: L-Threonine acetaldehyde-lyase (threonine aldolase, TA) is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes conversion of L-threonine or L-allo-threonine to glycine and acetaldehyde in a secondary glycine biosynthetic pathway. X-ray structures of Thermatoga maritima TA have been determined as the apo-enzyme at 1.8 A resolution and bound to substrate L-allo-threonine and product glycine at 1.9 and 2.0 A resolution, respectively. Despite low pairwise sequence identities, TA is a member of aspartate aminotransferase (AATase) fold family of PLP enzymes. The enzyme forms a 222 homotetramer with the PLP cofactor bound via a Schiff-base linkage to Lys199 within a domain interface. The structure reveals bound calcium and chloride ions that appear to contribute to catalysis and oligomerization, respectively. Although L-threonine and L-allo-threonine are substrates for T. maritima TA, enzymatic assays revealed a strong preference for L-allo-threonine. Structures of the external aldimines with substrate/product reveal a pair of histidines that may provide flexibility in substrate recognition. Variation in the threonine binding pocket may explain preferences for L-allo-threonine versus L-threonine among TA family members.
authors.affiliation: Laboratories of Molecular Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Clara L
authors.initials: CL
authors.lastname: Kielkopf
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D020134:Catalytic Domain; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry*; D007700:Kinetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D012545:Schiff Bases; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology
chemical_list: D046911:Macromolecular Substances; D012545:Schiff Bases; D012696:Glycine Hydroxymethyltransferase; D002118:Calcium