2c3c: Difference between revisions

Revision as of 17:44, 21 February 2008

2.01 ANGSTROM X-RAY CRYSTAL STRUCTURE OF A MIXED DISULFIDE BETWEEN COENZYME M AND NADPH-DEPENDENT OXIDOREDUCTASE 2-KETOPROPYL COENZYME M CARBOXYLASE

OverviewOverview

The structure of the mixed, enzyme-cofactor disulfide intermediate of ketopropyl-coenzyme M oxidoreductase/carboxylase has been determined by X-ray diffraction methods. Ketopropyl-coenzyme M oxidoreductase/carboxylase belongs to a family of pyridine nucleotide-containing flavin-dependent disulfide oxidoreductases, which couple the transfer of hydride derived from the NADPH to the reduction of protein cysteine disulfide. Ketopropyl-coenzyme M oxidoreductase/carboxylase, a unique member of this enzyme class, catalyzes thioether bond cleavage of the substrate, 2-ketopropyl-coenzyme M, and carboxylation of what is thought to be an enzyme-stabilized enolacetone intermediate. The mixed disulfide of 2-ketopropyl-coenzyme M oxidoreductase/carboxylase was captured through crystallization of the enzyme with the physiological products of the reaction, acetoacetate, coenzyme M, and NADP, and reduction of the crystals with dithiothreitol just prior to data collection. Density in the active-site environment consistent with acetone, the product of reductive decarboxylation of acetoacetate, was revealed in this structure in addition to a well-defined hydrophobic pocket or channel that could be involved in the access for carbon dioxide. The analysis of this structure and that of a coenzyme-M-bound form provides insights into the stabilization of intermediates, substrate carboxylation, and product release.

About this StructureAbout this Structure

2C3C is a Single protein structure of sequence from Xanthobacter autotrophicus with , , and as ligands. Active as 2-oxopropyl-CoM reductase (carboxylating), with EC number 1.8.1.5 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Mechanistic implications of the structure of the mixed-disulfide intermediate of the disulfide oxidoreductase, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase., Pandey AS, Nocek B, Clark DD, Ensign SA, Peters JW, Biochemistry. 2006 Jan 10;45(1):113-20. PMID:16388586

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 ==Overview==
-The structure of the mixed, enzyme-cofactor disulfide intermediate of, ketopropyl-coenzyme M oxidoreductase/carboxylase has been determined by, X-ray diffraction methods. Ketopropyl-coenzyme M, oxidoreductase/carboxylase belongs to a family of pyridine, nucleotide-containing flavin-dependent disulfide oxidoreductases, which, couple the transfer of hydride derived from the NADPH to the reduction of, protein cysteine disulfide. Ketopropyl-coenzyme M, oxidoreductase/carboxylase, a unique member of this enzyme class, catalyzes thioether bond cleavage of the substrate, 2-ketopropyl-coenzyme, M, and carboxylation of what is thought to be an enzyme-stabilized, enolacetone intermediate. The mixed disulfide of 2-ketopropyl-coenzyme M, oxidoreductase/carboxylase was captured through crystallization of the, enzyme with the physiological products of the reaction, acetoacetate, coenzyme M, and NADP, and reduction of the crystals with dithiothreitol, just prior to data collection. Density in the active-site environment, consistent with acetone, the product of reductive decarboxylation of, acetoacetate, was revealed in this structure in addition to a well-defined, hydrophobic pocket or channel that could be involved in the access for, carbon dioxide. The analysis of this structure and that of a, coenzyme-M-bound form provides insights into the stabilization of, intermediates, substrate carboxylation, and product release.
+The structure of the mixed, enzyme-cofactor disulfide intermediate of ketopropyl-coenzyme M oxidoreductase/carboxylase has been determined by X-ray diffraction methods. Ketopropyl-coenzyme M oxidoreductase/carboxylase belongs to a family of pyridine nucleotide-containing flavin-dependent disulfide oxidoreductases, which couple the transfer of hydride derived from the NADPH to the reduction of protein cysteine disulfide. Ketopropyl-coenzyme M oxidoreductase/carboxylase, a unique member of this enzyme class, catalyzes thioether bond cleavage of the substrate, 2-ketopropyl-coenzyme M, and carboxylation of what is thought to be an enzyme-stabilized enolacetone intermediate. The mixed disulfide of 2-ketopropyl-coenzyme M oxidoreductase/carboxylase was captured through crystallization of the enzyme with the physiological products of the reaction, acetoacetate, coenzyme M, and NADP, and reduction of the crystals with dithiothreitol just prior to data collection. Density in the active-site environment consistent with acetone, the product of reductive decarboxylation of acetoacetate, was revealed in this structure in addition to a well-defined hydrophobic pocket or channel that could be involved in the access for carbon dioxide. The analysis of this structure and that of a coenzyme-M-bound form provides insights into the stabilization of intermediates, substrate carboxylation, and product release.
 ==About this Structure==
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 [[Category: Single protein]]
 [[Category: Xanthobacter autotrophicus]]
-[[Category: Clark, D.D.]]
+[[Category: Clark, D D.]]
-[[Category: Ensign, S.A.]]
+[[Category: Ensign, S A.]]
 [[Category: Nocek, B.]]
-[[Category: Pandey, A.S.]]
+[[Category: Pandey, A S.]]
-[[Category: Peters, J.W.]]
+[[Category: Peters, J W.]]
 [[Category: ACN]]
 [[Category: COM]]
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 [[Category: redox-active center]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:30:55 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:25 2008''