3qvv

Crystal structure of Ancestral variant b9 of SULT 1A1 in complex with PAP and 3-CyC

spinqualitylabelsall models 3qvv, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qvv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3QV, A3P Related: 3qvu, 1ls6 Gene: SULT1A1, STP, STP1, OK/SW-cl.88 (Homo sapiens) Activity: Aryl sulfotransferase, with EC number 2.8.2.1 Resources: FirstGlance, OCA, RCSB, PDBsum Function [ST1A1_HUMAN] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk. Publication Abstract from PubMed Large libraries of randomly mutated genes are applied in directed evolution experiments in order to obtain sufficient variability. These libraries, however, contain mostly inactive variants, and the very low frequency of improved variants can only be isolated by high-throughput screening. Small but efficient libraries comprise an attractive alternative. Here, we describe the application of ancestral libraries-libraries based on mutations predicted by phylogenetic analysis and ancestral inference. We designed and constructed such libraries using serum paraoxonases and cytosolic sulfotransferases (SULTs) as model enzymes. Both of these enzyme families exhibit a range of activities in drug metabolism and detoxification of xenobiotics. The ancestral serum paraoxonase and SULT libraries were screened by low-throughput means, including HPLC, using substrates and/or reactions with which all family members exhibit low activity. The libraries showed a remarkably high frequency of highly polymorphic and functionally diverse variants. Screening of as few as 300 variants enabled the isolation of mutants with up to 50-fold higher activity than the starting point enzyme. Structural and kinetic characterizations of an evolved SULT variant show how few ancestral mutations reshaped the active site and modulated the enzyme's specificity. Ancestral libraries therefore comprise a means of focusing diversity to positions and mutations that readily trigger changes in substrate and/or reaction specificity, thereby facilitating the isolation of new enzyme variants for a variety of different substrates and reactions by medium-throughput or even low-throughput screens. Directed evolution of sulfotransferases and paraoxonases by ancestral libraries.,Alcolombri U, Elias M, Tawfik DS J Mol Biol. 2011 Aug 26;411(4):837-53. Epub 2011 Jun 24. PMID:21723874 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sulfotransferase

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