Open AccessCrystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy.
Author(s) -
Amy L. Swain,
Mariusz Jaskólski,
D. Housset,
Jayasimha Rao,
Alexander Wlodawer
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.4.1474
Subject(s) - homotetramer , escherichia coli , protein subunit , enzyme , active site , hydrolase , molecular replacement , chemistry , multiple isomorphous replacement , tetramer , asparaginase , crystallography , stereochemistry , biology , lymphoblastic leukemia , biochemistry , peptide sequence , leukemia , gene , genetics
The crystal structure of Escherichia coli asparaginase II (EC 3.5.1.1), a drug (Elspar) used for the treatment of acute lymphoblastic leukemia, has been determined at 2.3 A resolution by using data from a single heavy atom derivative in combination with molecular replacement. The atomic model was refined to an R factor of 0.143. This enzyme, active as a homotetramer with 222 symmetry, belongs to the class of alpha/beta proteins. Each subunit has two domains with unique topological features. On the basis of present structural evidence consistent with previous biochemical studies, we propose locations for the active sites between the N- and C-terminal domains belonging to different subunits and postulate a catalytic role for Thr-89.