Organic anion transporter

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OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles , and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3 , OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats , mice , rabbits , pigs , flounders , and nematodes.

Organic anion transporter

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about h OAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. Taking advantage of the AlphaFold 2 predicted structure of h OAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, h OAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability. The present model is made available to decipher the impact of any observed polymorphism and mutation on drug transport as well as to understand substrate binding modes. Major facilitator superfamily MFS proteins belong to the solute carrier SLC superfamily, one of the most important classes of membrane transporters. They can translocate a broad range of endogenous compounds and xenobiotics across cell membranes and play important pharmacological and physiological roles 1 , 2. MFS transporters can affect drug pharmacokinetics by modulating absorption, distribution and elimination 3 since they are involved in cellular influx or efflux.

Organic anions are a general term for a class of materials containing a carbon skeleton with a net negative charge under physiological pH conditions, organic anion transporter. Among the Oats, Oat1 as well as Oat3 has been highlighted by regulatory agencies as a key transporter involved in drug excretion and potential drug-drug interactions DDI 79 ,

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human Hs , mouse Mm and rat Rn. Show » « Hide. Organic anion transporters OATs are non-selective transporters prominent in the kidney, placenta and blood-brain barrier. Handb Exp Pharmacol , : Mol Aspects Med , 34 :

Federal government websites often end in. The site is secure. The organic anion transporter OAT subfamily, which constitutes roughly half of the SLC22 solute carrier 22 transporter family, has received a great deal of attention because of its role in handling of common drugs antibiotics, antivirals, diuretics, nonsteroidal anti-inflammatory drugs , toxins mercury, aristolochic acid , and nutrients vitamins, flavonoids. Oats are expressed in many tissues, including kidney, liver, choroid plexus, olfactory mucosa, brain, retina, and placenta. Recent metabolomics and microarray data from Oat1 [ Slc22a6 , originally identified as NKT novel kidney transporter ] and Oat3 Slc22a8 knockouts, as well as systems biology studies, indicate that this pathway plays a central role in the metabolism and handling of gut microbiome metabolites as well as putative uremic toxins of kidney disease.

Organic anion transporter

Federal government websites often end in. The site is secure. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver. To date, few articles have addressed these aspects of OAT and OATP structures, and we study further the similarities and differences in their structures, tissue distribution, substrates, and roles in liver diseases. Core tip: As important anion transporters, organic anion transporters OATs and organic anion transporter polypeptides OATPs have similar structures and transport substrates. In this paper, we study their structure, distribution, substrate of action, and regulatory mechanisms in various diseases of the liver. Organic anions are a general term for a class of materials containing a carbon skeleton with a net negative charge under physiological pH conditions.

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This will be important to explore in future work. As discussed below, Asp forms a salt bridge network between TM8 and TM10, which involves Lys and must break to drive transport. Transport of organic anions across the basolateral membrane of proximal tubule cells. Levels of uric acid, thought to function as an antioxidant, were altered in the Oat1 , Oat3 , and Urat1 originally Rst knockout mice The remaining mitochondria were enlarged and dysmorphic. Subjects Metabolism Structural biology. Subsequently, particles belonging to a putative Rn Oat1—Syb map were reconstituted by the second round of ab initio. Eur J Pharmacol. Organic anion-transporting polypeptides. Table 1 Cryo-EM data collection, refinement and validation statistics Full size table.

OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles , and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3 , OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys.

In addition, there is an association with PDZ domains Gender preferential expression of this gene has been noted with higher expression observed in female kidneys An integrated encyclopedia of DNA elements in the human genome. Similar to Oat1 23 , expression of Oat6 in rat olfactory epithelium can be induced by in vivo exposure to dexamethasone Email address Sign up. Building upon the concept of typical structural features for MFS proteins, tilt angles between TMHs and the lipid bilayer axis normal were monitored along MD simulations see Supplementary Fig. Sponsors list. The hepatitis-fibrosis-cirrhosis progression eventually leads to liver cancer. However, the GlyAla mutant had no discernible effect on tenofovir recognition Fig. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. At the nanoscale, substrate translocation is expected to follow alternating access involving at least three conformational states, namely the outward-facing OF , occluded and open inward-facing IF states 3. Several computational chemistry approaches have been used to study Oats and their substrates. Jumper, J. As described above, these three transporters share some substrate specificity, and sequence analysis indicates that all of the transporter genes in the cluster spanning about 1 Mb share a high degree of sequence similarity , raising the possibility that these novel transporters may also be able to handle small molecule organic anions similar to that of Oat1, Oat3, and Oat5 70 , The helices differ in the curvature at the helical ends, and the most pronounced variation between states was found for TMH11 and TMH8 Supplementary Fig.