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| | <StructureSection load='4l8w' size='340' side='right'caption='[[4l8w]], [[Resolution|resolution]] 2.39Å' scene=''> | | <StructureSection load='4l8w' size='340' side='right'caption='[[4l8w]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4l8w]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L8W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4l8w]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L8W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</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]] 2.39Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l7q|4l7q]], [[4l8f|4l8f]], [[4l8y|4l8y]], [[4l95|4l95]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ggh ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=4l8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l8w OCA], [https://pdbe.org/4l8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l8w RCSB], [https://www.ebi.ac.uk/pdbsum/4l8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l8w 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/Gamma-glutamyl_hydrolase Gamma-glutamyl hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.9 3.4.19.9] </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=4l8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l8w OCA], [http://pdbe.org/4l8w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l8w RCSB], [http://www.ebi.ac.uk/pdbsum/4l8w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l8w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6NY42_DANRE Q6NY42_DANRE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Gamma-glutamyl hydrolase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, C J]] | + | [[Category: Chen C-J]] |
| - | [[Category: Chuankhayan, P]] | + | [[Category: Chuankhayan P]] |
| - | [[Category: Fu, T F]] | + | [[Category: Fu T-F]] |
| - | [[Category: Kao, T T]] | + | [[Category: Kao T-T]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Sandwiched-like domain]]
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| Structural highlights
Function
Q6NY42_DANRE
Publication Abstract from PubMed
gamma-Glutamyl hydrolases (gammaGH) catalyze the hydrolysis of gamma-linked glutamate residues from the polyglutamyl of folates and antifolates, such as methotrexate (MTX), a widely used anticancer drug. We describe the first crystal structures of the endopeptidase-type gammaGH (zgammaGH) from zebrafish and the mutant complexes with MTX(Glu)5 and hydrolyzed MTX(Glu)1, revealing the complete set of key residues involved in hydrolysis as well as the substrate-binding subsites (-1 to +2). The side chain of Phe20 and the 6-methylpterin ring of MTX(Glu)5 invoke pi-pi interactions to promote distinct concerted conformational alterations involving approximately 90 degrees rotations in the complexes with the zgammaGH-C108A and zgammaGH-H218N mutant proteins. The structural geometries of the MTX(Glu)5 and hydrolyzed MTX(Glu)1 in the mutant complexes differ significantly from those of the previously known MTX(Glu)1, providing polymorphic information. Together with the structural comparison and the activity analysis, these results shed light on the catalytic mechanism and substrate recognition of zgammaGH and other gamma-glutamyl hydrolases.
Structural insights into the hydrolysis and polymorphism of methotrexate polyglutamate by zebrafish gamma-glutamyl hydrolase.,Chuankhayan P, Kao TT, Lin CC, Guan HH, Nakagawa A, Fu TF, Chen CJ J Med Chem. 2013 Oct 10;56(19):7625-35. doi: 10.1021/jm401013e. Epub 2013 Sep 27. PMID:24028568[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chuankhayan P, Kao TT, Lin CC, Guan HH, Nakagawa A, Fu TF, Chen CJ. Structural insights into the hydrolysis and polymorphism of methotrexate polyglutamate by zebrafish gamma-glutamyl hydrolase. J Med Chem. 2013 Oct 10;56(19):7625-35. doi: 10.1021/jm401013e. Epub 2013 Sep 27. PMID:24028568 doi:http://dx.doi.org/10.1021/jm401013e
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