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

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms7874· OSTI ID:1178476
 [1];  [2];  [2];  [1];  [1];  [2];  [2];  [3];  [4]
  1. Iowa State Univ., IA (United States). Dept. of Chemistry
  2. Iowa State Univ., IA (United States). Dept. of Physics and Astronomy
  3. Argonne National Laboratory, IL (United States). NE-CAT and Dept. of chemistry and Chemical BIology
  4. Iowa State Univ., IA (United States). Dept. of Chemistry and Dept. of Physics and Astronomy

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1178476
Journal Information:
Nature Communications, Vol. 6; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 30 works
Citation information provided by
Web of Science

References (42)

HKL2MAP : a graphical user interface for macromolecular phasing with SHELX programs journal September 2004
Genome sequence of the ubiquitous hydrocarbon-degrading marine bacterium Alcanivorax borkumensis journal July 2006
Substructure solution with SHELXD journal September 2002
Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum journal December 1997
Replacement of the folC gene, encoding folylpolyglutamate synthetase-dihydrofolate synthetase in Escherichia coli, with genes mutagenized in vitro. journal March 1992
Structure-based mechanism for Na+/melibiose symport by MelB journal January 2014
Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport journal September 2010
Functional Cloning and Characterization of the Multidrug Efflux Pumps NorM from Neisseria gonorrhoeae and YdhE from Escherichia coli journal June 2008
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
Structures of a Na+-coupled, substrate-bound MATE multidrug transporter journal January 2013
PHENIX : building new software for automated crystallographic structure determination journal October 2002
Plasmodium falciparum: a paradigm for alternative folate biosynthesis in diverse microorganisms? journal November 2008
The multidrug efflux protein NorM is a prototype of a new family of transporters journal January 1999
The CCP4 suite programs for protein crystallography journal September 1994
Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future journal June 2014
Valence Screening of Water in Protein Crystals Reveals Potential Na+Binding Sites journal February 1996
The ion transporter superfamily journal December 2003
Crystal Structures of CusC Review Conformational Changes Accompanying Folding and Transmembrane Channel Formation journal January 2014
Use of glycerol-cryoprotected Lactobacillus casei for microbiological assay of folic acid. journal May 1982
Historical and Regulatory Perspectives on the Treatment Effect of Antibacterial Drugs for Community‐Acquired Pneumonia journal December 2008
The biosynthesis of folic acidVI. Enzymatic conversion of carbon atom 8 of guanosine triphosphate to formic acid journal March 1966
Competence-specific induction ofrecAis required for full recombination proficiency during transformation inStreptococcus pneumoniae journal January 1998
Escherichia coli abg Genes Enable Uptake and Cleavage of the Folate Catabolite p-Aminobenzoyl-Glutamate journal February 2007
Global Topology Analysis of the Escherichia coli Inner Membrane Proteome journal May 2005
Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. journal July 1994
Coot model-building tools for molecular graphics journal November 2004
Maximum-likelihood density modification using pattern recognition of structural motifs journal November 2001
The Biosynthesis of Folic Acid journal September 1961
Characterization of Mutations That Allow p -Aminobenzoyl-Glutamate Utilization byEscherichia coli journal December 1998
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products journal May 2000
Nucleotide sequence of Escherichia coli pabA and its evolutionary relationship to trp (G) D journal August 1983
The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery journal June 2002
Identification of a cell envelope protein (MtrF) involved in hydrophobic antimicrobial resistance in Neisseria gonorrhoeae journal November 2002
Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization journal March 1997
Regulation of mtrF Expression in Neisseria gonorrhoeae and Its Role in High-Level Antimicrobial Resistance journal May 2005
Crystal Structure of Escherichia coli CusC, the Outer Membrane Component of a Heavy Metal Efflux Pump journal January 2011
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
Phaser crystallographic software journal July 2007
The Biosynthesis of Folic Acid journal February 1962
The Biosynthesis of Folic Acid journal January 1964
The Biosynthesis of Folic Acid journal March 1969
The Biosynthesis of Folic Acid journal June 1970

Cited By (10)

Structural models of the NaPi-II sodium-phosphate cotransporters journal September 2018
Elevating the alternating-access model journal March 2016
Structure and Mechanism of the Divalent Anion/Na+ Symporter journal January 2019
Energetic evolution of cellular Transportomes journal May 2018
Structure and function of the divalent anion/Na+ symporter from Vibrio cholerae and a humanized variant journal April 2017
The bacterial dicarboxylate transporter VcINDY uses a two-domain elevator-type mechanism journal February 2016
Convergent evolution of the arginine deiminase pathway: the ArcD and ArcE arginine/ornithine exchangers journal November 2016
Energetic Evolution of Cellular Transportomes posted_content November 2017
Family resemblances: A common fold for some dimeric ion-coupled secondary transporters journal October 2015
Shaping the lipid composition of bacterial membranes for membrane protein production journal August 2019

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