The x-ray crystal structure of lysine-2,3-aminomutase from Clostridium subterminale

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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-Å resolution by single-wavelength anomalous dispersion methods on a l -selenomethionine-substituted complex of LAM with [4Fe–4S] 2+ , PLP, SAM, and l -α-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 β/α 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 -α-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.