2V6G

Structure of Progesterone 5beta-Reductase from Digitalis Lanata in complex with NADP

2V6G の概要

• エントリーDOI: 10.2210/pdb2v6g/pdb
• 関連するPDBエントリー: 2V6F
• 分子名称: PROGESTERONE 5-BETA-REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: tyrosine-dependent oxidoreductase, oxidoreductase, sdr, reductase, cardenolides, cardiac glycosides
• 由来する生物種: DIGITALIS LANATA (FOXGLOVE)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42129.62

構造登録者

Thorn, A.,Egerer-Sieber, C.,Jaeger, C.,Herl, V.,Mueller-Uri, F.,Kreis, W.,Muller, Y.A. (登録日: 2007-07-18, 公開日: 2007-11-20, 最終更新日: 2024-05-01)

主引用文献

Thorn, A.,Egerer-Sieber, C.,Jaeger, C.,Herl, V.,Mueller-Uri, F.,Kreis, W.,Muller, Y.A.
The Crystal Structure of Progesterone 5{Beta}-Reductase from Digitalis Lanata Defines a Novel Class of Short Chain Dehydrogenases/Reductases.
J.Biol.Chem., 283:17260-, 2008

PubMed Abstract: Progesterone 5beta-reductase (5beta-POR) catalyzes the stereospecific reduction of progesterone to 5beta-pregnane-3,20-dione and is a key enzyme in the biosynthetic pathway of cardenolides in Digitalis (foxglove) plants. Sequence considerations suggested that 5beta-POR is a member of the short chain dehydrogenase/reductase (SDR) family of proteins but at the same time revealed that the sequence motifs that in standard SDRs contain the catalytically important residues are missing. Here we present crystal structures of 5beta-POR from Digitalis lanata in complex with NADP(+) at 2.3A and without cofactor bound at 2.4A resolution together with a model of a ternary complex consisting of 5beta-POR, NADP(+), and progesterone. Indeed, 5beta-POR displays the fold of an extended SDR. The architecture of the active site is, however, unprecedented because none of the standard catalytic residues are structurally conserved. A tyrosine (Tyr-179) and a lysine residue (Lys-147) are present in the active site, but they are displayed from novel positions and are part of novel sequence motifs. Mutating Tyr-179 to either alanine or phenylalanine completely abolishes the enzymatic activity. We propose that the distinct topology reflects the fact that 5beta-POR reduces a conjugated double bond in a steroid substrate via a 1-4 addition mechanism and that this requires a repositioning of the catalytically important residues. Our observation that the sequence motifs that line the active site are conserved in a number of bacterial and plant enzymes of yet unknown function leads us to the proposition that 5beta-POR defines a novel class of SDRs.

PubMed: 18032383
DOI: 10.1074/JBC.M706185200

実験手法

X-RAY DIFFRACTION (2.3 Å)