The structure of Neurospora crassa 3-carboxy-cis,cis-muconate lactonizing enzyme, a beta propeller cycloisomerase

Structure. 2002 Apr;10(4):483-92. doi: 10.1016/s0969-2126(02)00744-x.

Abstract

Muconate lactonizing enzymes (MLEs) convert cis,cis-muconates to muconolactones in microbes as part of the beta-ketoadipate pathway; some also dehalogenate muconate derivatives of xenobiotic haloaromatics. There are three different MLE classes unrelated by evolution. We present the X-ray structure of a eukaryotic MLE, Neurospora crassa 3-carboxy-cis,cis-muconate lactonizing enzyme (NcCMLE) at 2.5 A resolution, with a seven-bladed beta propeller fold. It is related neither to bacterial MLEs nor to other beta propeller enzymes, but is structurally similar to the G protein beta subunit. It reveals a novel metal-independent cycloisomerase motif unlike the bacterial metal cofactor MLEs. Together, the bacterial MLEs and NcCMLE structures comprise a striking structural example of functional convergence in enzymes for 1,2-addition-elimination of carboxylic acids. NcCMLE and bacterial MLEs may enhance the reaction rate differently: the former by electrophilic catalysis and the latter by electrostatic stabilization of the enolate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Binding Sites
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Intramolecular Lyases / chemistry*
  • Intramolecular Lyases / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Mutagenesis, Site-Directed
  • Neurospora crassa / enzymology*
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary*
  • Protein Subunits
  • Sequence Alignment

Substances

  • Bacterial Proteins
  • Fungal Proteins
  • Protein Subunits
  • Intramolecular Lyases
  • 3-carboxy-cis-cis-muconate cyclase

Associated data

  • PDB/1JOF