7ld9
From Proteopedia
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| - | ==== | + | ==Structure of human GGT1 in complex with ABBA== |
| - | <StructureSection load='7ld9' size='340' side='right'caption='[[7ld9]]' scene=''> | + | <StructureSection load='7ld9' size='340' side='right'caption='[[7ld9]], [[Resolution|resolution]] 1.42Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ld9]] 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=7LD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LD9 FirstGlance]. <br> |
| - | </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=7ld9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ld9 OCA], [https://pdbe.org/7ld9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ld9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ld9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ld9 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XU7:(2S)-2-amino-4-boronobutanoic+acid'>XU7</scene>, <scene name='pdbligand=XUJ:(2R)-2-amino-4-boronobutanoic+acid'>XUJ</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=7ld9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ld9 OCA], [https://pdbe.org/7ld9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ld9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ld9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ld9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/GGT1_HUMAN GGT1_HUMAN] Gamma-glutamyl transpeptidase deficiency. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GGT1_HUMAN GGT1_HUMAN] Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Catalyzes the transfer of the glutamyl moiety of glutathione to amino acids and dipeptide acceptors. Alternatively, glutathione can be hydrolyzed to give Cys-Gly and gamma glutamate. Isoform 3 seems to be inactive.<ref>PMID:7689219</ref> <ref>PMID:20622017</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inhibitors of gamma-glutamyl transpeptidase (GGT1, aka gamma-glutamyl transferase) are needed for the treatment of cancer, cardiovascular illness and other diseases. Compounds that inhibit GGT1 have been evaluated in the clinic, but no inhibitor has successfully demonstrated specific and systemic GGT1 inhibition. All have severe side effects. L-2-amino-4âboronobutanoic acid (l-ABBA), a glutamate analog, is the most potent GGT1 inhibitor in vitro. In this study, we have solved the crystal structure of human GGT1 (hGGT1) with ABBA bound in the active site. The structure was interrogated to identify interactions between the enzyme and the inhibitor. Based on these data, a series of novel ABBA analogs were designed and synthesized. Their inhibitory activity against the hydrolysis and transpeptidation activities of hGGT1 were determined. The lead compounds were crystalized with hGGT1 and the structures solved. The kinetic data and structures of the complexes provide new insights into the critical role of protein structure dynamics in developing compounds for inhibition of hGGT1. | ||
| + | |||
| + | Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase.,Nguyen L, Schultz DC, Terzyan SS, Rezaei M, Songb J, Li C, You Y, Hanigan MH Bioorg Med Chem. 2022 Nov 1;73:116986. doi: 10.1016/j.bmc.2022.116986. Epub 2022 , Aug 27. PMID:36208545<ref>PMID:36208545</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ld9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Hanigan M]] |
| + | [[Category: Terzyan SS]] | ||
Revision as of 07:41, 8 March 2023
Structure of human GGT1 in complex with ABBA
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