Structural Insight into Dihydrodipicolinate Reductase from Corybebacterium glutamicum for Lysine Biosynthesis.
Dihydrodipicolinate reductase is an enzyme that converts dihydrodipicolinate to tetrahydrodipicolinate using an NAD(P)H cofactor in L-lysine biosynthesis. To increase the understanding of the molecular mechanisms of lysine biosynthesis, we determined the crystal structure of dihydrodipicolinate reductase from Corynebacterium glutamicum (CgDapB). CgDapB functions as a tetramer, and each protomer is composed of two domains, an Nterminal domain and a C-terminal domain. The N-terminal domain mainly contributes to nucleotide binding, whereas the C-terminal domain is involved in substrate binding. We elucidated the mode of cofactor binding to CgDapB by determining the crystal structure of the enzyme in complex with NADP(+) and found that CgDapB utilizes both NADH and NADPH as cofactors. Moreover, we determined the substrate binding mode of the enzyme based on the coordination mode of two sulfate ions in our structure. Compared with Mycobacterium tuberculosis DapB in complex with its cofactor and inhibitor, we propose that the domain movement for active site constitution occurs when both cofactor and substrate bind to the enzyme.
School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
Hye-Young
HY
Sagong
School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
Kyung-Jin
KJ
Kim
D000595:Amino Acid Sequence; D001665:Binding Sites; D055162:Biocatalysis; D048230:Corynebacterium glutamicum / Q000201:enzymology* / Q000378:metabolism; D018360:Crystallography, X-Ray; D050746:Dihydrodipicolinate Reductase / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000096:biosynthesis*; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D009243:NAD; D009249:NADP; D010088:Oxidoreductases; D050746:Dihydrodipicolinate Reductase; D008239:Lysine
Corynebacterium glutamicum; L-lysine; dihydrodipicolinate reductase