Structures of open (R) and close (T) states of prephenate dehydratase (PDT)--implication of allosteric regulation by L-phenylalanine

J Struct Biol. 2008 Apr;162(1):94-107. doi: 10.1016/j.jsb.2007.11.009. Epub 2007 Nov 29.

Abstract

The enzyme prephenate dehydratase (PDT) converts prephenate to phenylpyruvate in L-phenylalanine biosynthesis. PDT is allosterically regulated by L-Phe and other amino acids. We report the first crystal structures of PDT from Staphylococcus aureus in a relaxed (R) state and PDT from Chlorobium tepidum in a tense (T) state. The two enzymes show low sequence identity (27.3%) but the same prototypic architecture and domain organization. Both enzymes are tetramers (dimer of dimers) in crystal and solution while a PDT dimer can be regarded as a basic catalytic unit. The N-terminal PDT domain consists of two similar subdomains with a cleft in between, which hosts the highly conserved active site. In one PDT dimer two clefts are aligned to form an extended active site across the dimer interface. Similarly at the interface two ACT regulatory domains create two highly conserved pockets. Upon binding of the L-Phe inside the pockets, PDT transits from an open to a closed conformation.

Publication types

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

MeSH terms

  • Allosteric Regulation / drug effects
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Chlorobium / enzymology*
  • Crystallography, X-Ray
  • Dimerization
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Phenylalanine / chemistry
  • Phenylalanine / pharmacology
  • Prephenate Dehydratase / chemistry*
  • Prephenate Dehydratase / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Staphylococcus aureus / enzymology*

Substances

  • Bacterial Proteins
  • Phenylalanine
  • Prephenate Dehydratase

Associated data

  • PDB/2QMW
  • PDB/2QMX