PDBsum entry 2cfc

Oxidoreductase

PDB id: 2cfc

Contents

Protein chains

250 a.a. *

Ligands

NAD ×4

KPC ×4

Waters ×915

* Residue conservation analysis

PDB id:

2cfc

Name:

Oxidoreductase

Title:

Structural basis for stereo selectivity in the (r)- and (s)- hydroxypropylethane thiosulfonate dehydrogenases

Structure:

2-(r)-hydroxypropyl-com dehydrogenase. Chain: a, b, c, d. Synonym: r-hpcd, r-hpcdh, aliphatic epoxide carboxylation component iii. Ec: 1.1.1.268

Source:

Xanthobacter autotrophicus. Organism_taxid: 78245. Strain: py2

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.80Å R-factor: 0.197 R-free: 0.227

Authors:

A.M.Krishnakumar,B.P.Nocek,D.D.Clark,S.A.Ensign,J.W.Peters

Key ref:

A.M.Krishnakumar et al. (2006). Structural basis for stereoselectivity in the (R)- and (S)-hydroxypropylthioethanesulfonate dehydrogenases. Biochemistry, 45, 8831-8840. PubMed id: 16846226

Date:

19-Feb-06 Release date: 26-Jul-06

Protein chains

Q56840  (HCDR_XANP2) -  2-(R)-hydroxypropyl-CoM dehydrogenase from Xanthobacter autotrophicus (strain ATCC BAA-1158 / Py2)

Seq: 250 a.a.

Struc: 250 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.268 - 2-(R)-hydroxypropyl-CoM dehydrogenase.
• Pathway: Epoxide Carboxylation
• Reaction: (R)-2-hydroxypropyl-coenzyme M + NAD⁺ = 2-oxopropyl-coenzyme M + NADH + H⁺

(R)-2-hydroxypropyl-coenzyme M + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = 2-oxopropyl-coenzyme M + NADH + H(+)

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

Added reference

Biochemistry 45:8831-8840 (2006)

PubMed id: 16846226

Structural basis for stereoselectivity in the (R)- and (S)-hydroxypropylthioethanesulfonate dehydrogenases.

A.M.Krishnakumar, B.P.Nocek, D.D.Clark, S.A.Ensign, J.W.Peters.

ABSTRACT

Epoxide metabolism in Xanthobacter autotrophicus Py2 results in the conversion of epoxypropane to acetoacetate. Epoxide metabolism is initiated by the nucleophilic addition of coenzyme M to the (R)- and (S)-enantiomers of epoxypropane which forms the respective enantiomers of 2-hydroxypropyl-coenyme M. The (R)- and (S)-enantiomers of 2-hydroxypropyl coenzyme are oxidized to the achiral product 2-ketopropyl-CoM by two stereoselective dehydrogenases. The dehydrogenases catalyzing these reactions, termed (R)-hydroxypropyl-coenzyme M dehydrogenase (R-HPCDH) and (S)-hydroxypropyl-coenzyme M dehydrogenase (S-HPCDH), are NAD(+)-dependent enzymes belonging to the short chain dehydrogenase/reductase (SDR) family of enzymes. In this study, the crystal structure of R-HPCDH cocrystallized in the presence of (S)-hydroxypropyl-coenzyme M has been determined using X-ray diffraction methods and refined to 1.8 A resolution. The structure of R-HPCDH is tetrameric and stabilized by the interaction of the terminal carboxylates of each subunit with divalent metal ions. The structure of the presumed product-bound state reveals that binding interactions between the negatively charged oxygen atoms of the sulfonate moiety have striking similarities to sulfonate interactions observed in the previously determined structure of 2-ketopropyl-CoM oxidoreductase/carboxylase, highlighting the utility of coenzyme M as a carrier molecule in the pathway. The key elements of the aforementioned interactions are electrostatic interactions between the sulfonate oxygen atoms and two arginine residues (R152 and R196) of R-HPCDH. The comparison of the structure of R-HPCDH with a homology model of S-HPCDH provides a structural basis for a mechanism of substrate specificity in which the binding of the substrate sulfonate moiety at distinct sites on each stereoselective enzyme directs the orientation of the appropriate substrate enantiomer for hydride abstraction.