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| | ==Crystal structure of mouse glyoxalase I in complexed with 18-beta-glycyrrhetinic acid== | | ==Crystal structure of mouse glyoxalase I in complexed with 18-beta-glycyrrhetinic acid== |
| - | <StructureSection load='4pv5' size='340' side='right' caption='[[4pv5]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4pv5' size='340' side='right'caption='[[4pv5]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pv5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PV5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PV5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pv5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PV5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBW:(3BETA,5BETA,14BETA)-3-HYDROXY-11-OXOOLEAN-12-EN-29-OIC+ACID'>CBW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBW:(3BETA,5BETA,14BETA)-3-HYDROXY-11-OXOOLEAN-12-EN-29-OIC+ACID'>CBW</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glo1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4pv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pv5 OCA], [https://pdbe.org/4pv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pv5 RCSB], [https://www.ebi.ac.uk/pdbsum/4pv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pv5 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lactoylglutathione_lyase Lactoylglutathione lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.5 4.4.1.5] </span></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=4pv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pv5 OCA], [http://pdbe.org/4pv5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pv5 RCSB], [http://www.ebi.ac.uk/pdbsum/4pv5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pv5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LGUL_MOUSE LGUL_MOUSE]] Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (By similarity). | + | [https://www.uniprot.org/uniprot/LGUL_MOUSE LGUL_MOUSE] Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (By similarity). |
| | <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 4pv5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4pv5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glyoxalase 3D structures|Glyoxalase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lactoylglutathione lyase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hu, X P]] | + | [[Category: Hu XP]] |
| - | [[Category: Li, C]] | + | [[Category: Li C]] |
| - | [[Category: Zhai, J]] | + | [[Category: Zhai J]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Zhang, L P]] | + | [[Category: Zhang LP]] |
| - | [[Category: Zhao, Y N]] | + | [[Category: Zhao YN]] |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| Structural highlights
Function
LGUL_MOUSE Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (By similarity).
Publication Abstract from PubMed
AIM: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. METHODS: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-beta-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 A resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. RESULTS: A natural compound 18-beta-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 mumol/L and 0.93 mumol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 mumol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the gamma-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. CONCLUSION: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors.
Structural basis for 18-beta-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor.,Zhang H, Huang Q, Zhai J, Zhao YN, Zhang LP, Chen YY, Zhang RW, Li Q, Hu XP Acta Pharmacol Sin. 2015 Sep;36(9):1145-50. doi: 10.1038/aps.2015.59. Epub 2015, Aug 17. PMID:26279158[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang H, Huang Q, Zhai J, Zhao YN, Zhang LP, Chen YY, Zhang RW, Li Q, Hu XP. Structural basis for 18-beta-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor. Acta Pharmacol Sin. 2015 Sep;36(9):1145-50. doi: 10.1038/aps.2015.59. Epub 2015, Aug 17. PMID:26279158 doi:http://dx.doi.org/10.1038/aps.2015.59
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