3-D structure of serum paraoxonase 1 sheds light on its activity, stability, solubility and crystallizability.
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.
Harel
Michal
M
Weizmann Institute of Science, Rehovot, Israel.
Brumshtein
Boris
B
Meged
Ran
R
Dvir
Hay
H
Ravelli
Raimond B G
RB
McCarthy
Andrew
A
Toker
Lilly
L
Silman
Israel
I
Sussman
Joel L
JL
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
D013928:Thromboxane A2; D043303:Aryldialkylphosphatase