The crystal structure of an odorant binding protein from Anopheles gambiae: Evidence for a common ligand release mechanism

Mark Wogulis, Tania Morgan, Yuko Ishida, Walter S. Leal, David K. Wilson

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5 Å crystal structure of AgamOBP1, an odorant binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a dimer with a unique binding pocket consisting of a continuous tunnel running through both subunits of the dimer and occupied by a PEG molecule. We demonstrate that AgamOBP1 undergoes a pH dependent conformational change that is associated with reduced ligand binding. A predominance of acid-labile hydrogen bonds involving the C-terminal loop suggests a mechanism in which a drop in pH causes C-terminal loop to open, leaving the binding tunnel solvent exposed, thereby lowering binding affinity for ligand. Because proteins from two distantly related insects also undergo a pH dependent conformational change involving the C-terminus that is associated with reduced ligand affinity, our results suggest a common mechanism for OBP activity.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume339
Issue number1
DOIs
StatePublished - Jan 6 2006

Fingerprint

Anopheles gambiae
Crystal structure
Ligands
Culicidae
Dimers
Tunnels
Africa South of the Sahara
Staphylococcal Protein A
Polyethylene glycols
Malaria
Insects
Hydrogen
Hydrogen bonds
Proteins
Molecules
Acids
odorant-binding protein

Keywords

  • Anopheles gambiae
  • Crystal structure
  • Ligand binding
  • Malaria
  • Olfaction
  • pH dependent binding

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The crystal structure of an odorant binding protein from Anopheles gambiae : Evidence for a common ligand release mechanism. / Wogulis, Mark; Morgan, Tania; Ishida, Yuko; Leal, Walter S.; Wilson, David K.

In: Biochemical and Biophysical Research Communications, Vol. 339, No. 1, 06.01.2006, p. 157-164.

Research output: Contribution to journalArticle

Wogulis, Mark ; Morgan, Tania ; Ishida, Yuko ; Leal, Walter S. ; Wilson, David K. / The crystal structure of an odorant binding protein from Anopheles gambiae : Evidence for a common ligand release mechanism. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 339, No. 1. pp. 157-164.
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