title: The x-ray crystal structure of lysine-2,3-aminomutase from Clostridium subterminale.
abstract: The x-ray crystal structure of the pyridoxal-5'-phosphate (PLP), S-adenosyl-L-methionine (SAM), and [4Fe-4S]-dependent lysine-2,3-aminomutase (LAM) of Clostridium subterminale has been solved to 2.1-A resolution by single-wavelength anomalous dispersion methods on a L-selenomethionine-substituted complex of LAM with [4Fe-4S]2+, PLP, SAM, and L-alpha-lysine, a very close analog of the active Michaelis complex. The unit cell contains a dimer of hydrogen-bonded, domain-swapped dimers, the subunits of which adopt a fold that contains all three cofactors in a central channel defined by six beta/alpha structural units. Zinc coordination links the domain-swapped dimers. In each subunit, the solvent face of the channel is occluded by an N-terminal helical domain, with the opposite end of the channel packed against the domain-swapped subunit. Hydrogen-bonded ionic contacts hold the external aldimine of PLP and L-alpha-lysine in position for abstraction of the 3-pro-R hydrogen of lysine by C5' of SAM. The structure of the SAM/[4Fe-4S] complex confirms and extends conclusions from spectroscopic studies of LAM and shows selenium in Se-adenosyl-L-selenomethionine poised to ligate the unique iron in the [4Fe-4S] cluster upon electron transfer and radical formation. The chain fold in the central domain is in part analogous to other radical-SAM enzymes.
authors.affiliation: Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, 1710 University Avenue, Madison, WI 53726, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Lepore
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Ruzicka
authors.forename: Perry A
authors.initials: PA
authors.lastname: Frey
authors.forename: Dagmar
authors.initials: D
authors.lastname: Ringe
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003013:Clostridium / Q000201:enzymology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D019751:Intramolecular Transferases / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011732:Pyridoxal Phosphate / Q000737:chemistry; D012436:S-Adenosylmethionine / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D011732:Pyridoxal Phosphate; D012436:S-Adenosylmethionine; D019751:Intramolecular Transferases; C021518:lysine 2,3-aminomutase; D015032:Zinc