Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

Nat Commun. 2015 Apr 20:6:6874. doi: 10.1038/ncomms7874.

Abstract

The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alcanivoraceae / drug effects
  • Alcanivoraceae / genetics
  • Alcanivoraceae / metabolism*
  • Anti-Infective Agents / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Folic Acid / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Bacterial / physiology
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Sulfamethazine / metabolism

Substances

  • Anti-Infective Agents
  • Bacterial Proteins
  • Carrier Proteins
  • Sulfamethazine
  • Folic Acid

Associated data

  • PDB/4R0C