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. Structured summary of protein interactionsDHDPRbindstoDHDPR by molecular sieving(View interaction).DHDPRbindstoDHDPR by dynamic light scattering(View interaction).DHDPRbindstoDHDPR by X-ray crystallography(View interaction).