Title: The crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism Wang X, Wang CS, Tang J, Dyda F, Zhang XC Ref: Structure, 5:1209, 1997 : PubMed
BACKGROUND:
The intestinally located pancreatic enzyme, bile salt activated lipase (BAL), possesses unique activities for digesting different kinds of lipids. It also differs from other lipases in a requirement of bile salts for activity. A structure-based explanation for these unique properties has not been reached so far due to the absence of a three-dimensional structure.
RESULTS:
The crystal structures of bovine BAL and its complex with taurocholate have been determined at 2.8 A resolution. The overall structure of BAL belongs to the alpha/beta hydrolase fold family. Two bile salt binding sites were found in each BAL molecule within the BAL-taurocholate complex structure. One of these sites is located close to a hairpin loop near the active site. Upon the binding of taurocholate, this loop becomes less mobile and assumes a different conformation. The other bile salt binding site is located remote from the active site. In both structures, BAL forms similar dimers with the active sites facing each other.
CONCLUSIONS:
Bile salts activate BAL by binding to a relatively short ten-residue loop near the active site, and stabilize the loop in an open conformation. Presumably, this conformational change leads to the formation of the substrate-binding site, as suggested from kinetic data. The BAL dimer observed in the crystal structure may also play a functional role under physiological conditions.
Representative scheme of Cholesterol_esterase structure and an image from PDBsum server
Databases
PDB-Sum
1AQL Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
1AQLFold classification based on Structure-Structure alignment of Proteins - FSSP server
