1H61

Structure of Pentaerythritol Tetranitrate Reductase in complex with prednisone

Summary for 1H61

• Entry DOI: 10.2210/pdb1h61/pdb
• Related: 1H50 1H51 1H60 1H62
• Descriptor: PENTAERYTHRITOL TETRANITRATE REDUCTASE, FLAVIN MONONUCLEOTIDE, 17,21-DIHYDROXYPREGNA-1,4-DIENE-3,11,20-TRIONE, ... (4 entities in total)
• Functional Keywords: steroid binding, oxidoreductase, flavoenzyme
• Biological source: ENTEROBACTER CLOACAE
• Total number of polymer chains: 1
• Total formula weight: 40218.77

Authors

Barna, T.M.,Moody, P.C.E. (deposition date: 2001-06-04, release date: 2001-07-05, Last modification date: 2023-12-13)

Primary citation

Barna, T.M.,Khan, H.,Bruce, N.C.,Barsukov, I.,Scrutton, N.S.,Moody, P.C.
Crystal Structure of Pentaerythritol Tetranitrate Reductase: "Flipped" Binding Geometries for Steroid Substrates in Different Redox States of the Enzyme
J.Mol.Biol., 310:433-, 2001

PubMed Abstract: Pentaerythritol tetranitrate reductase (PETN reductase) degrades high explosive molecules including nitrate esters, nitroaromatics and cyclic triazine compounds. The enzyme also binds a variety of cyclic enones, including steroids; some steroids act as substrates whilst others are inhibitors. Understanding the basis of reactivity with cyclic enones requires structural information for the enzyme and key complexes formed with steroid substrates and inhibitors. The crystal structure of oxidised and reduced PETN reductase at 1.5 A resolution establishes a close structural similarity to the beta/alpha-barrel flavoenzyme, old yellow enzyme. In complexes of oxidised PETN reductase with progesterone (an inhibitor), 1,4-androstadiene-3,17-dione and prednisone (both substrates) the steroids are stacked over the si-face of the flavin in an orientation different from that reported for old yellow enzyme. The specifically reducible 1,2 unsaturated bonds in 1,4-androstadiene-3,17-dione and prednisone are not optimally aligned with the flavin N5 in oxidised enzyme complexes. These structures suggest either relative "flipping" or shifting of the steroid with respect to the flavin when bound in different redox forms of the enzyme. Deuterium transfer from nicotinamide coenzyme to 1,4-androstadiene-3,17-dione via the enzyme bound FMN indicates 1alpha addition at the steroid C2 atom. These studies rule out lateral motion of the steroid and indicate that the steroid orientation is "flipped" in different redox states of the enzyme.

PubMed: 11428899
DOI: 10.1006/JMBI.2001.4779

Experimental method

X-RAY DIFFRACTION (1.4 Å)