1h60: Difference between revisions

Revision as of 13:57, 21 February 2008

STRUCTURE OF PENTAERYTHRITOL TETRANITRATE REDUCTASE IN COMPLEX WITH PROGESTERONE

OverviewOverview

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.

About this StructureAbout this Structure

1H60 is a Single protein structure of sequence from Enterobacter cloacae with and as ligands. Known structural/functional Sites: and . Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of pentaerythritol tetranitrate reductase: "flipped" binding geometries for steroid substrates in different redox states of the enzyme., Barna TM, Khan H, Bruce NC, Barsukov I, Scrutton NS, Moody PC, J Mol Biol. 2001 Jul 6;310(2):433-47. PMID:11428899

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 ==Overview==
-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.
+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.
 ==About this Structure==
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 [[Category: steroid binding]]
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+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:57:47 2008''