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| | ==Crystal Structure Of AKR1B10 Complexed With NADP+ And Epalrestat== | | ==Crystal Structure Of AKR1B10 Complexed With NADP+ And Epalrestat== |
| - | <StructureSection load='4jih' size='340' side='right' caption='[[4jih]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4jih' size='340' side='right'caption='[[4jih]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jih]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JIH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jih]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JIH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPR:{5-[(2E)-2-METHYL-3-PHENYLPROP-2-EN-1-YLIDENE]-4-OXO-2-THIOXO-1,3-THIAZOLIDIN-3-YL}ACETIC+ACID'>EPR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EPR:{5-[(2E)-2-METHYL-3-PHENYLPROP-2-EN-1-YLIDENE]-4-OXO-2-THIOXO-1,3-THIAZOLIDIN-3-YL}ACETIC+ACID'>EPR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jii|4jii]], [[4jir|4jir]], [[4gqg|4gqg]], [[4gq0|4gq0]], [[4i5x|4i5x]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jih OCA], [https://pdbe.org/4jih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jih RCSB], [https://www.ebi.ac.uk/pdbsum/4jih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jih ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1B10, AKR1B11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4jih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jih OCA], [http://pdbe.org/4jih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jih RCSB], [http://www.ebi.ac.uk/pdbsum/4jih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jih ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AK1BA_HUMAN AK1BA_HUMAN]] Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.<ref>PMID:18087047</ref> | + | [https://www.uniprot.org/uniprot/AK1BA_HUMAN AK1BA_HUMAN] Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.<ref>PMID:18087047</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4jih" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4jih" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aldo-keto reductase 3D structures|Aldo-keto reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chen, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Hu, X]] | + | [[Category: Chen K]] |
| - | [[Category: Structural genomic]] | + | [[Category: Hu X]] |
| - | [[Category: Zhai, J]] | + | [[Category: Zhai J]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Zhang, L]] | + | [[Category: Zhang L]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Zhao Y]] |
| - | [[Category: Zheng, X]] | + | [[Category: Zheng X]] |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
Function
AK1BA_HUMAN Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.[1]
Publication Abstract from PubMed
The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation.
Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111).,Zhang L, Zhang H, Zhao Y, Li Z, Chen S, Zhai J, Chen Y, Xie W, Wang Z, Li Q, Zheng X, Hu X FEBS Lett. 2013 Oct 4. pii: S0014-5793(13)00726-6. doi:, 10.1016/j.febslet.2013.09.031. PMID:24100137[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gallego O, Ruiz FX, Ardevol A, Dominguez M, Alvarez R, de Lera AR, Rovira C, Farres J, Fita I, Pares X. Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20764-9. Epub 2007 Dec 17. PMID:18087047
- ↑ Zhang L, Zhang H, Zhao Y, Li Z, Chen S, Zhai J, Chen Y, Xie W, Wang Z, Li Q, Zheng X, Hu X. Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111). FEBS Lett. 2013 Oct 4. pii: S0014-5793(13)00726-6. doi:, 10.1016/j.febslet.2013.09.031. PMID:24100137 doi:http://dx.doi.org/10.1016/j.febslet.2013.09.031
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