title: Crystallization and preliminary structural analysis of Bacillus subtilis adenylosuccinate lyase, an enzyme implicated in infantile autism.
abstract: Adenylosuccinate lyase (ASL) from Bacillus subtilis has been crystallized and structural analysis by X-ray diffraction is in progress. ASL is a 200-kDa homotetramer that catalyzes two distinct steps of de novo purine biosynthesis leading to the formation of AMP and IMP; both steps involve the beta-elimination of fumarate. A single point mutation in the human ASL gene has been linked to mental retardation with autistic features. In addition, ASL plays an important role in the bioprocessing of anti-HIV therapeutics. B subtilis ASL, which shares 30% sequence identity and 70% sequence similarity with human ASL, has been crystallized and data to 3.3 A have been collected at 100 K. The space group is P6(1)22 or P6(5)22 with a = b = 129.4 A; the length of the c-axis varies between 275 and 290 A, depending on the crystal. An analysis of solvent content indicates a dimer in the asymmetric unit, although a self-rotation function and an analysis of native Pattersons failed to identify unambiguously the location of any noncrystallographic symmetry axes. Structure determination by isomorphous replacement is in progress.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles 90095, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Redinbo
authors.forename: S M
authors.initials: SM
authors.lastname: Eide
authors.forename: R L
authors.initials: RL
authors.lastname: Stone
authors.forename: J E
authors.initials: JE
authors.lastname: Dixon
authors.forename: T O
authors.initials: TO
authors.lastname: Yeates
mesh_terms: D000264:Adenylosuccinate Lyase / Q000737:chemistry*; D001321:Autistic Disorder / Q000201:enzymology*; D001412:Bacillus subtilis / Q000201:enzymology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D011687:Purines / Q000096:biosynthesis
chemical_list: D011687:Purines; D000264:Adenylosuccinate Lyase; C030985:purine