title: Structure and nucleotide specificity of Staphylococcus aureus dihydrodipicolinate reductase (DapB).
abstract: Lysine biosynthesis proceeds by the nucleotide-dependent reduction of dihydrodipicolinate (DHDP) to tetrahydrodipicolinate (THDP) by dihydrodipicolinate reductase (DHDPR). The S. aureus DHDPR structure reveals different conformational states of this enzyme even in the absence of a substrate or nucleotide-cofactor. Despite lacking a conserved basic residue essential for NADPH interaction, S. aureus DHDPR differs from other homologues as NADPH is a more preferred co-factor than NADH. The structure provides a rationale-Lys35 compensates for the co-factor site mutation. These observations are significant for bi-ligand inhibitor design that relies on ligand-induced conformational changes as well as co-factor specificity for this important drug target.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
authors.forename: Tavarekere S
authors.initials: TS
authors.lastname: Girish
authors.forename: Vikas
authors.initials: V
authors.lastname: Navratna
authors.forename: B
authors.initials: B
authors.lastname: Gopal
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D050746:Dihydrodipicolinate Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D009249:NADP; D050746:Dihydrodipicolinate Reductase