2v6f

Structure of Progesterone 5beta-Reductase from Digitalis Lanata

spinqualitylabelsall models 2v6f, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v6f is a 1 chain structure with sequence from Digitalis lanata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 5BPOR_DIGLA Involved in cardenolide biosynthesis. Catalyzes the stereospecific conversion of progesterone to 5-beta-pregnane-3,20-dione. Can use progesterone, testosterone, 4-androstene-3,17-dione, cortisol and cortisone as substrates, but not pregnenolone, 21-OH-pregnenolone or isoprogesterone. NADPH could not be replaced by NADH. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The crystal structure of progesterone 5beta-reductase from Digitalis lanata defines a novel class of short chain dehydrogenases/reductases.,Thorn A, Egerer-Sieber C, Jager CM, Herl V, Muller-Uri F, Kreis W, Muller YA J Biol Chem. 2008 Jun 20;283(25):17260-9. Epub 2007 Nov 21. PMID:18032383 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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