Crystal structure of dihydrodipicolinate reductase (PaDHDPR) from Paenisporosarcina sp. TG-14: structural basis for NADPH preference as a cofactor
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- Crystal structure of dihydrodipicolinate reductase (PaDHDPR) from Paenisporosarcina sp. TG-14: structural basis for NADPH preference as a cofactor
- Other Titles
- 남극 빙하미생물 유래 dihydrodipicolinate reductase 효소의 삼차구조연구: 조효소로써 NADPH를 선호하는 구조적 이유 설명
- Lee, Chang Woo
Lee, Jun Hyuck
Hak Jun Kim
Hyun Ho Park
Lee, Sung Gu
- Multidisciplinary Sciences
- Paenisporosarcina sp. TG-14; X-ray crystallography; crystal structure; dihydrodipicolinate reductase
- Issue Date
- Lee, Chang Woo, et al. 2018. Crystal structure of dihydrodipicolinate reductase (PaDHDPR) from Paenisporosarcina sp. TG-14: structural basis for NADPH preference as a cofactor., SCIENTIFIC REPORTS 8(1): 1-12.
- Dihydrodipicolinate reductase (DHDPR) is a key enzyme in the diaminopimelate- and lysine-synthesis pathways that reduces DHDP to tetrahydrodipicolinate. Although DHDPR uses both NADPH and NADH as a cofactor, the structural basis for cofactor specificity and preference remains unclear. Here, we report that Paenisporosarcina sp. TG-14 PaDHDPR has a strong preference for NADPH over NADH, as determined by isothermal titration calorimetry and enzymatic activity assays. We determined the crystal structures of PaDHDPR alone, with its competitive inhibitor (dipicolinate), and the ternary complex of the enzyme with dipicolinate and NADPH, with results showing that only the ternary complex had a fully closed conformation and suggesting that binding of both substrate and nucleotide cofactor is required for enzymatic activity. Moreover, NADPH binding induced local conformational changes in the N-terminal long loop (residues 34？59) of PaDHDPR, as the His35 and Lys36 residues in this loop interacted with the 2′-phosphate group of NADPH, possibly accounting for the strong preference of PaDHDPR for NADPH. Mutation of these residues revealed reduced NADPH binding and enzymatic activity, confirming their importance in NADPH binding. These findings provide insight into the mechanism of action and cofactor selectivity of this important bacterial enzyme.
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