title: 3-D structure of serum paraoxonase 1 sheds light on its activity, stability, solubility and crystallizability.
abstract: Serum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the "good cholesterol"), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 A resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1's active site and suggests possible mechanisms for its catalytic activity on certain substrates.
authors.affiliation: Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Harel
authors.forename: Boris
authors.initials: B
authors.lastname: Brumshtein
authors.forename: Ran
authors.initials: R
authors.lastname: Meged
authors.forename: Hay
authors.initials: H
authors.lastname: Dvir
authors.forename: Raimond B G
authors.initials: RB
authors.lastname: Ravelli
authors.forename: Andrew
authors.initials: A
authors.lastname: McCarthy
authors.forename: Lilly
authors.initials: L
authors.lastname: Toker
authors.forename: Israel
authors.initials: I
authors.lastname: Silman
authors.forename: Joel L
authors.initials: JL
authors.lastname: Sussman
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood / Q000737:chemistry*; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D006801:Humans; D008968:Molecular Conformation; D013928:Thromboxane A2
chemical_list: D013928:Thromboxane A2; D043303:Aryldialkylphosphatase