<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>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 Å 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.</p></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 Å 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.

3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and Crystallizability

Weizmann Institute of Science, Rehovot, Israel

European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France

Archives of Industrial Hygiene and Toxicology

Serum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases....

3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and Crystallizability

Publicado en línea: 03 oct 2007

Páginas: 347 - 353

DOI: https://doi.org/10.2478/v10004-007-0028-0

Palabras clave
katalitički mehanizam, usmjerena evolucija, varijante koje tvore kristale

This content is open access.

3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and Crystallizability

Publicado en línea: 03 oct 2007

Páginas: 347 - 353

DOI: https://doi.org/10.2478/v10004-007-0028-0

Palabras clavekatalitički mehanizam, usmjerena evolucija, varijante koje tvore kristale

This content is open access.

Palabras clave
katalitički mehanizam, usmjerena evolucija, varijante koje tvore kristale