Cutting off functional loops from homodimeric enzyme superoxide dismutase 1 (SOD1) leaves monomeric β-barrels.

ABSTRACT: Demetallation of the homodimeric enzyme Cu/Zn-superoxide dismutase (SOD1) is known to unleash pronounced dynamic motions in the long active-site loops that comprise almost a third of the folded structure. The resulting apo species, which shows increased propensity to aggregate, stands out as the prime disease precursor in amyotrophic lateral sclerosis (ALS). Even so, the detailed structural properties of the apoSOD1 framework have remained elusive and controversial. In this study, we examine the structural interplay between the central apoSOD1 barrel and the active-site loops by simply cutting them off; loops IV and VII were substituted with short Gly-Ala-Gly linkers. The results show that loop removal breaks the dimer interface and leads to soluble, monomeric β-barrels with high structura

SUBMITTER: Danielsson J 

PROVIDER: S-EPMC3190884 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature