Crystal structure of the catalytic domain of human bile salt activated lipase.
Bile-salt activated lipase (BAL) is a pancreatic enzyme that digests a variety of lipids in the small intestine. A distinct property of BAL is its dependency on bile salts in hydrolyzing substrates of long acyl chains or bulky alcoholic motifs. A crystal structure of the catalytic domain of human BAL (residues 1-538) with two surface mutations (N186D and A298D), which were introduced in attempting to facilitate crystallization, has been determined at 2.3 A resolution. The crystal form belongs to space group P2(1)2(1)2(1) with one monomer per asymmetric unit, and the protein shows an alpha/beta hydrolase fold. In the absence of bound bile salt molecules, the protein possesses a preformed catalytic triad and a functional oxyanion hole. Several surface loops around the active site are mobile, including two loops potentially involved in substrate binding (residues 115-125 and 270-285).
Terzyan
S
S
Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Wang
C S
CS
Downs
D
D
Hunter
B
B
Zhang
X C
XC
D000595:Amino Acid Sequence; D001647:Bile Acids and Salts / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006801:Humans; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D001647:Bile Acids and Salts; D008049:Lipase