title: The structure of Neurospora crassa 3-carboxy-cis,cis-muconate lactonizing enzyme, a beta propeller cycloisomerase.
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.
authors.affiliation: Institute of Biotechnology, Research Program in Structural Biology and Biophysics, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Kajander
authors.forename: Michael C
authors.initials: MC
authors.lastname: Merckel
authors.forename: Andrew
authors.initials: A
authors.lastname: Thompson
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Deacon
authors.forename: Paul
authors.initials: P
authors.lastname: Mazur
authors.forename: John W
authors.initials: JW
authors.lastname: Kozarich
authors.forename: Adrian
authors.initials: A
authors.lastname: Goldman
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry; D019753:Intramolecular Lyases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D009492:Neurospora crassa / Q000201:enzymology*; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D005656:Fungal Proteins; D021122:Protein Subunits; D019753:Intramolecular Lyases; C019831:3-carboxy-cis-cis-muconate cyclase