3vw9

From Proteopedia

(Difference between revisions)

Current revision

Human Glyoxalase I with an N-hydroxypyridone inhibitor

Structural highlights

3vw9 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.
Method:	X-ray diffraction, Resolution 1.47Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LGUL_HUMAN 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.^[1]

Publication Abstract from PubMed

We conducted a high throughput screening for glyoxalase I (GLO1) inhibitors and identified 4,6-diphenyl-N-hydroxypyridone as a lead compound. Using a binding model of the lead and public X-ray coordinates of GLO1 enzymes complexed with glutathione analogues, we designed 4-(7-azaindole)-substituted 6-phenyl-N-hydroxypyridones. 7-Azaindole's 7-nitrogen was expected to interact with a water network, resulting in an interaction with the protein. We validated this inhibitor design by comparing its structure-activity relationship (SAR) with that of corresponding indole derivatives, by analyzing the binding mode with X-ray crystallography and by evaluating its thermodynamic binding parameters.

Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors.,Chiba T, Ohwada J, Sakamoto H, Kobayashi T, Fukami TA, Irie M, Miura T, Ohara K, Koyano H Bioorg Med Chem Lett. 2012 Dec 15;22(24):7486-9. doi: 10.1016/j.bmcl.2012.10.045., Epub 2012 Oct 17. PMID:23122816^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ de Hemptinne V, Rondas D, Toepoel M, Vancompernolle K. Phosphorylation on Thr-106 and NO-modification of glyoxalase I suppress the TNF-induced transcriptional activity of NF-kappaB. Mol Cell Biochem. 2009 May;325(1-2):169-78. doi: 10.1007/s11010-009-0031-7. Epub , 2009 Feb 6. PMID:19199007 doi:http://dx.doi.org/10.1007/s11010-009-0031-7
↑ Chiba T, Ohwada J, Sakamoto H, Kobayashi T, Fukami TA, Irie M, Miura T, Ohara K, Koyano H. Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7486-9. doi: 10.1016/j.bmcl.2012.10.045., Epub 2012 Oct 17. PMID:23122816 doi:http://dx.doi.org/10.1016/j.bmcl.2012.10.045

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vw9"

Categories: Homo sapiens | Large Structures | Fukami TA | Irie M | Matsuura T

@@ Line 3: / Line 3: @@
 <StructureSection load='3vw9' size='340' side='right'caption='[[3vw9]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3vw9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VW9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3vw9]] is a 2 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=3VW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VW9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=HPJ:1-HYDROXY-6-[1-(3-METHOXYPROPYL)-1H-PYRROLO[2,3-B]PYRIDIN-5-YL]-4-PHENYLPYRIDIN-2(1H)-ONE'>HPJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.47&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLO1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=HPJ:1-HYDROXY-6-[1-(3-METHOXYPROPYL)-1H-PYRROLO[2,3-B]PYRIDIN-5-YL]-4-PHENYLPYRIDIN-2(1H)-ONE'>HPJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Lactoylglutathione_lyase Lactoylglutathione lyase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3vw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vw9 OCA], [https://pdbe.org/3vw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vw9 RCSB], [https://www.ebi.ac.uk/pdbsum/3vw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vw9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/LGUL_HUMAN LGUL_HUMAN]] 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.<ref>PMID:19199007</ref>
+[https://www.uniprot.org/uniprot/LGUL_HUMAN LGUL_HUMAN] 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.<ref>PMID:19199007</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Lactoylglutathione lyase]]
 [[Category: Large Structures]]
-[[Category: Fukami, T A]]
+[[Category: Fukami TA]]
-[[Category: Irie, M]]
+[[Category: Irie M]]
-[[Category: Matsuura, T]]
+[[Category: Matsuura T]]
-[[Category: Glyoxalase]]
-[[Category: Lyase-lyase inhibitor complex]]

3vw9

From Proteopedia

Current revision

Human Glyoxalase I with an N-hydroxypyridone inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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