1v04
From Proteopedia
serum paraoxonase by directed evolution
Structural highlights
FunctionPON1_RABIT Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification.[1] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMembers of the serum paraoxonase (PON) family have been identified in mammals and other vertebrates, and in invertebrates. PONs exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve agents. PON1 and PON3 reside on high-density lipoprotein (HDL, 'good cholesterol') and are involved in the prevention of atherosclerosis. We describe the first crystal structure of a PON family member, a variant of PON1 obtained by directed evolution, at a resolution of 2.2 A. PON1 is a six-bladed beta-propeller with a unique active site lid that is also involved in HDL binding. The three-dimensional structure and directed evolution studies permit a detailed description of PON1's active site and catalytic mechanism, which are reminiscent of secreted phospholipase A2, and of the routes by which PON family members diverged toward different substrate and reaction selectivities. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes.,Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS Nat Struct Mol Biol. 2004 May;11(5):412-9. Epub 2004 Apr 18. PMID:15098021[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
Categories: Homo sapiens | Large Structures | Mus musculus | Oryctolagus cuniculus | Rattus rattus | Aharoni A | Brumshtein B | Dvir H | Gaidukov L | Harel M | Khersonsky O | McCarthy A | Meged R | Ravelli RBG | Silman I | Sussman JL | Tawfik DS | Toker L | Yagur S