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Crystallization and preliminary structural analysis of Bacillus subtilis adenylosuccinate lyase, an enzyme implicated in infantile autism
Author(s) -
Redinbo Matthew R.,
Eide Sithumini M.,
Stone Randy L.,
Dixon Jack E.,
Yeates Todd O.
Publication year - 1996
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560050425
Subject(s) - bacillus subtilis , enzyme , lyase , autism , crystallization , biochemistry , biology , chemistry , genetics , medicine , bacteria , organic chemistry , psychiatry
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 β ‐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 Å; the length of the c‐axis varies between 275 and 290 Å, 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.