4l7q: Difference between revisions
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==Crystal structure of gamma glutamyl hydrolase (wild-type) from zebrafish== | |||
<StructureSection load='4l7q' size='340' side='right'caption='[[4l7q]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4l7q]] 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=4L7Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L7Q FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4l7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l7q OCA], [https://pdbe.org/4l7q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l7q RCSB], [https://www.ebi.ac.uk/pdbsum/4l7q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l7q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6NY42_DANRE Q6NY42_DANRE] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24028568</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4l7q" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen C-J]] | |||
[[Category: Chuankhayan P]] | |||
[[Category: Fu T-F]] | |||
[[Category: Kao T-T]] | |||
Latest revision as of 17:33, 8 November 2023
Crystal structure of gamma glutamyl hydrolase (wild-type) from zebrafishCrystal structure of gamma glutamyl hydrolase (wild-type) from zebrafish
Structural highlights
FunctionPublication Abstract from PubMedgamma-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
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