1ARZ

ESCHERICHIA COLI DIHYDRODIPICOLINATE REDUCTASE IN COMPLEX WITH NADH AND 2,6 PYRIDINE DICARBOXYLATE

1ARZ の概要

• エントリーDOI: 10.2210/pdb1arz/pdb
• 分子名称: DIHYDRODIPICOLINATE REDUCTASE, PHOSPHATE ION, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, reductase, lysine biosynthesis, nadh binding
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P04036
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117845.37

構造登録者

Scapin, G.,Reddy, S.G.,Zheng, R.,Blanchard, J.S. (登録日: 1997-08-08, 公開日: 1998-10-14, 最終更新日: 2024-05-22)

主引用文献

Scapin, G.,Reddy, S.G.,Zheng, R.,Blanchard, J.S.
Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase in complex with NADH and the inhibitor 2,6-pyridinedicarboxylate.
Biochemistry, 36:15081-15088, 1997

PubMed Abstract: Dihydrodipicolinate reductase catalyzes the NAD(P)H-dependent reduction of the alpha,beta-unsaturated cyclic imine dihydrodipicolinate to form the cyclic imine tetrahydrodipicolinate. The enzyme is a component of the biosynthetic pathway that leads to diaminopimelate and lysine in bacteria and higher plants. Because these pathways are unique to microorganisms and plants, they may represent attractive targets for new antimicrobial or herbicidal compounds. The three-dimensional structure of the ternary complex of Escherichia coli dihydrodipicolinate reductase with NADH and the inhibitor 2,6-pyridinedicarboxylate has been solved using a combination of molecular replacement and noncrystallographic symmetry averaging procedures and refined against 2.6 A resolution data to a crystallographic R-factor of 21.4% (Rfree is 29.7%). The native enzyme is a 120 000 molecular weight tetramer of identical subunits. The refined crystallographic model contains a tetramer, three molecules of NADH, three molecules of inhibitor, one phosphate ion, and 186 water molecules per asymmetric unit. Each subunit consists of two domains connected by two flexible hinge regions. While three of the four subunits of the tetramer have a closed conformation, in which the nicotinamide ring of the cofactor bound to the N-terminal domain and the reducible carbon of the substrate bound to the substrate binding domain are about 3.5 A away, the fourth subunit is unliganded and shows an open conformation, suggesting that the enzyme undergoes a major conformational change upon binding of both substrates. The residues involved in binding of the inhibitor and the residues involved in catalysis have been identified on the basis of the three-dimensional structure. Site-directed mutants have been used to further characterize the role of these residues in binding and catalysis. A chemical mechanism for the enzyme, based on these and previously reported data, is proposed.

PubMed: 9398235
DOI: 10.1021/bi9719915

実験手法

X-RAY DIFFRACTION (2.6 Å)