5epg
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human aldehyde oxidase SNP S1271L== | |
| + | <StructureSection load='5epg' size='340' side='right' caption='[[5epg]], [[Resolution|resolution]] 3.39Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5epg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EPG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uhw|4uhw]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5epg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5epg OCA], [http://pdbe.org/5epg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5epg RCSB], [http://www.ebi.ac.uk/pdbsum/5epg PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/AOXA_HUMAN AOXA_HUMAN]] Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.<ref>PMID:20444863</ref> <ref>PMID:22031625</ref> <ref>PMID:22279051</ref> <ref>PMID:22522748</ref> <ref>PMID:22996261</ref> <ref>PMID:23857892</ref> <ref>PMID:7786031</ref> <ref>PMID:9224775</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Aldehyde oxidase (AOX1) is an enzyme with a broad substrate specificity, catalyzing the oxidation of a wide range of endogenous and exogenous aldehydes as well as N-heterocyclic aromatic compounds. In humans, the enzyme has been recognized with an emerging importance in phase I drug metabolism. However, the true physiological function of AOX1 in mammals is still unknown. Further, numerous single-nucleotide polymorphisms (SNPs) have been identified in human AOX1. SNPs are a major source of inter-individual variability in the human population and SNP-based amino acid exchanges in AOX1 were reported to modulate the catalytic function of the enzyme in either a positive or negative fashion. For the reliable analysis of the effect of amino acid exchanges in human proteins, the existence of reproducible expression systems for the production of active protein in ample amounts for kinetic, spectroscopic and crystallographic studies is required. In our study we report an optimized expression system for hAOX1 in Escherichia coli using a codon-optimized construct. The codon-optimization resulted in an up to 15-fold increase of protein production and a simplified purification procedure. Using the optimized expression system three SNPs were studied, resulting in amino acid changes C44W, G1269R and S1271L. In addition, the crystal structure of the S1271L SNP was solved. We demonstrate that the recombinant enzyme can be used for future studies to exploit the role of AOX in drug metabolism, and for the identification and synthesis of new drugs targeting AOX in combination with crystallographic and modeling studies. | ||
| - | + | Optimization of the expression of Human Aldehyde Oxidase for Investigations of Single Nucleotide Polymorphisms.,Foti A, Hartmann T, Coelho C, Santos-Silva T, Romao MJ, Leimkuhler S Drug Metab Dispos. 2016 Feb 3. pii: dmd.115.068395. PMID:26842593<ref>PMID:26842593</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5epg" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Coelho, C]] | [[Category: Coelho, C]] | ||
| - | [[Category: Romao, M | + | [[Category: Romao, M J]] |
| + | [[Category: Santos-Silva, T]] | ||
| + | [[Category: Drug metabolism]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Snp]] | ||
Revision as of 02:43, 21 February 2016
Human aldehyde oxidase SNP S1271L
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