Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases.

ABSTRACT: Crystal structures of two bacterial metal (Zn²⁺)-dependent d-fructose-1,6-bisphosphate (FBP) aldolases in complex with substrate, analogues, and triose-P reaction products were determined to 1.5-2.0 Å resolution. The ligand complexes cryotrapped in native or mutant Helicobacter pylori aldolase crystals enabled a novel mechanistic description of FBP C3-C4 bond cleavage. The reaction mechanism uses active site remodeling during the catalytic cycle, implicating relocation of the Zn²⁺ cofactor that is mediated by conformational changes of active site loops. Substrate binding initiates conformational changes triggered upon P1 phosphate binding, which liberates the Zn²⁺-chelating His-180, allowing it to act as a general base for the proton abstraction at t

SUBMITTER: Jacques B 

PROVIDER: S-EPMC5961046 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature