8c5d: Difference between revisions

Revision as of 04:02, 25 May 2023

Glutathione transferase P1-1 from Mus musculus

Structural highlights

8c5d is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CA, CL, GOL, GTB, NA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GSTP1_MOUSE Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Can metabolize 1-chloro-2,4-dinitrobenzene. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration (By similarity).

Publication Abstract from PubMed

Multidrug resistance is a significant barrier that makes anticancer therapies less effective. Glutathione transferases (GSTs) are involved in multidrug resistance mechanisms and play a significant part in the metabolism of alkylating anticancer drugs. The purpose of this study was to screen and select a lead compound with high inhibitory potency against the isoenzyme GSTP1-1 from Mus musculus (MmGSTP1-1). The lead compound was selected following the screening of a library of currently approved and registered pesticides that belong to different chemical classes. The results showed that the fungicide iprodione [3-(3,5-dichlorophenyl)-2,4-dioxo-N-propan-2-ylimidazolidine-1-carboxamide] exhibited the highest inhibition potency (IotaC(50) = 11.3 +/- 0.5 muMu) towards MmGSTP1-1. Kinetics analysis revealed that iprodione functions as a mixed-type inhibitor towards glutathione (GSH) and non-competitive inhibitor towards 1-chloro-2,4-dinitrobenzene (CDNB). X-ray crystallography was used to determine the crystal structure of MmGSTP1-1 at 1.28 A resolution as a complex with S-(p-nitrobenzyl)glutathione (Nb-GSH). The crystal structure was used to map the ligand-binding site of MmGSTP1-1 and to provide structural data of the interaction of the enzyme with iprodione using molecular docking. The results of this study shed light on the inhibition mechanism of MmGSTP1-1 and provide a new compound as a potential lead structure for future drug/inhibitor development.

Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1.,Kupreienko O, Pouliou F, Konstandinidis K, Axarli I, Douni E, Papageorgiou AC, Labrou NE Biomolecules. 2023 Mar 29;13(4):613. doi: 10.3390/biom13040613. PMID:37189361^[1]

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

References

↑ Kupreienko O, Pouliou F, Konstandinidis K, Axarli I, Douni E, Papageorgiou AC, Labrou NE. Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1. Biomolecules. 2023 Mar 29;13(4):613. PMID:37189361 doi:10.3390/biom13040613

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kupreienko O, Pouliou F, Konstandinidis K, Axarli I, Douni E, Papageorgiou AC, Labrou NE. Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1. Biomolecules. 2023 Mar 29;13(4):613. PMID:37189361 doi:10.3390/biom13040613

[1]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8c5d is ON HOLD  until Paper Publication
+==Glutathione transferase P1-1 from Mus musculus==
+<StructureSection load='8c5d' size='340' side='right'caption='[[8c5d]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8c5d]] 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=8C5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C5D FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTB:S-(P-NITROBENZYL)GLUTATHIONE'>GTB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=8c5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c5d OCA], [https://pdbe.org/8c5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c5d RCSB], [https://www.ebi.ac.uk/pdbsum/8c5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c5d ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/GSTP1_MOUSE GSTP1_MOUSE] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Can metabolize 1-chloro-2,4-dinitrobenzene. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Multidrug resistance is a significant barrier that makes anticancer therapies less effective. Glutathione transferases (GSTs) are involved in multidrug resistance mechanisms and play a significant part in the metabolism of alkylating anticancer drugs. The purpose of this study was to screen and select a lead compound with high inhibitory potency against the isoenzyme GSTP1-1 from Mus musculus (MmGSTP1-1). The lead compound was selected following the screening of a library of currently approved and registered pesticides that belong to different chemical classes. The results showed that the fungicide iprodione [3-(3,5-dichlorophenyl)-2,4-dioxo-N-propan-2-ylimidazolidine-1-carboxamide] exhibited the highest inhibition potency (IotaC(50) = 11.3 +/- 0.5 muMu) towards MmGSTP1-1. Kinetics analysis revealed that iprodione functions as a mixed-type inhibitor towards glutathione (GSH) and non-competitive inhibitor towards 1-chloro-2,4-dinitrobenzene (CDNB). X-ray crystallography was used to determine the crystal structure of MmGSTP1-1 at 1.28 A resolution as a complex with S-(p-nitrobenzyl)glutathione (Nb-GSH). The crystal structure was used to map the ligand-binding site of MmGSTP1-1 and to provide structural data of the interaction of the enzyme with iprodione using molecular docking. The results of this study shed light on the inhibition mechanism of MmGSTP1-1 and provide a new compound as a potential lead structure for future drug/inhibitor development.
-Authors: Papageorgiou, A.C.
+Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1.,Kupreienko O, Pouliou F, Konstandinidis K, Axarli I, Douni E, Papageorgiou AC, Labrou NE Biomolecules. 2023 Mar 29;13(4):613. doi: 10.3390/biom13040613. PMID:37189361<ref>PMID:37189361</ref>
-Description: Glutathione transferase P1-1 from Mus musculus
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Papageorgiou, A.C]]
+<div class="pdbe-citations 8c5d" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Papageorgiou AC]]

8c5d: Difference between revisions

Revision as of 04:02, 25 May 2023

Glutathione transferase P1-1 from Mus musculus

Structural highlights

Function

Publication Abstract from PubMed

References

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