PDBsum entry 2c3c

Oxidoreductase

PDB id: 2c3c

Contents

Protein chains

522 a.a. *

Ligands

COM ×2

FAD ×2

ACN ×2

NAP ×2

Waters ×711

* Residue conservation analysis

PDB id:

2c3c

Name:

Oxidoreductase

Title:

2.01 angstrom x-ray crystal structure of a mixed disulfide between coenzyme m and NADPH-dependent oxidoreductase 2-ketopropyl coenzyme m carboxylase

Structure:

2-oxopropyl-com reductase. Chain: a, b. Synonym: nadph\:2-ketopropyl coenzyme m carboxylase/ oxidoreductase, 2-kpcc, aliphatic epoxide carboxylation component ii. Ec: 1.8.1.5

Source:

Xanthobacter autotrophicus. Organism_taxid: 78245. Strain: py2. Atcc: 35674

Biol. unit:

Dimer (from PDB file)

Resolution:

2.15Å R-factor: 0.181 R-free: 0.226

Authors:

A.S.Pandey,B.Nocek,D.D.Clark,S.A.Ensign,J.W.Peters

Key ref:

A.S.Pandey et al. (2006). Mechanistic implications of the structure of the mixed-disulfide intermediate of the disulfide oxidoreductase, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase. Biochemistry, 45, 113-120. PubMed id: 16388586 DOI: 10.1021/bi051518o

Date:

05-Oct-05 Release date: 12-Dec-05

Protein chains

Q56839  (XECC_XANP2) -  2-oxopropyl-CoM reductase, carboxylating from Xanthobacter autotrophicus (strain ATCC BAA-1158 / Py2)

Seq: 523 a.a.

Struc: 522 a.a.

Enzyme reactions

• Enzyme class: E.C.1.8.1.5 - 2-oxopropyl-CoM reductase (carboxylating).
• Pathway: Epoxide Carboxylation
• Reaction: coenzyme M + acetoacetate + NADP⁺ = 2-oxopropyl-coenzyme M + CO2 + NADPH

coenzyme M (Bound ligand (Het Group name = ACN) matches with 57.14% similarity) + acetoacetate (Bound ligand (Het Group name = COM) corresponds exactly) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 2-oxopropyl-coenzyme M + CO2 + NADPH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/bi051518o

Biochemistry 45:113-120 (2006)

PubMed id: 16388586

Mechanistic implications of the structure of the mixed-disulfide intermediate of the disulfide oxidoreductase, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase.

A.S.Pandey, B.Nocek, D.D.Clark, S.A.Ensign, J.W.Peters.

ABSTRACT

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.