1AE1

TROPINONE REDUCTASE-I COMPLEX WITH NADP

1AE1 の概要

• エントリーDOI: 10.2210/pdb1ae1/pdb
• 分子名称: TROPINONE REDUCTASE-I, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: oxidoreductase, tropane alkaloid biosynthesis, reduction of tropinone to tropine, short-chain dehydrogenase
• 由来する生物種: Datura stramonium (jimsonweed)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60782.64

構造登録者

Nakajima, K.,Yamashita, A.,Akama, H.,Nakatsu, T.,Kato, H.,Hashimoto, T.,Oda, J.,Yamada, Y. (登録日: 1997-10-23, 公開日: 1998-11-18, 最終更新日: 2024-02-07)

主引用文献

Nakajima, K.,Yamashita, A.,Akama, H.,Nakatsu, T.,Kato, H.,Hashimoto, T.,Oda, J.,Yamada, Y.
Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold.
Proc.Natl.Acad.Sci.USA, 95:4876-4881, 1998

PubMed Abstract: A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.

PubMed: 9560196
DOI: 10.1073/pnas.95.9.4876

実験手法

X-RAY DIFFRACTION (2.4 Å)