Biological channeling of a reactive intermediate in the bifunctional enzyme DmpFG

Natalie E. Smith, Alice Vrielink, Paul V. Attwood, Ben Corry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


It has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD + is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD +. We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD + but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site.

Original languageEnglish
Pages (from-to)868-877
Number of pages10
JournalBiophysical Journal
Issue number4
Publication statusPublished - 22 Feb 2012
Externally publishedYes


Dive into the research topics of 'Biological channeling of a reactive intermediate in the bifunctional enzyme DmpFG'. Together they form a unique fingerprint.

Cite this