5luc: Difference between revisions
New page: '''Unreleased structure''' The entry 5luc is ON HOLD Authors: Giardina, G., Cutruzzola', F., Cellini, B., Borri Voltattorni, C., Montioli, R. Description: Crystal structure of the D183... |
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The entry | ==Crystal structure of the D183N variant of human Alanine:Glyoxylate Aminotransferase major allele (AGT-Ma) at 1.8 Angstrom; internal aldimine with PLP in the active site== | ||
<StructureSection load='5luc' size='340' side='right'caption='[[5luc]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5luc]] is a 8 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=5LUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LUC 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=5luc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5luc OCA], [https://pdbe.org/5luc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5luc RCSB], [https://www.ebi.ac.uk/pdbsum/5luc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5luc ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/AGT1_HUMAN AGT1_HUMAN] Primary hyperoxaluria type 1. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AGT1_HUMAN AGT1_HUMAN] Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification (PubMed:10960483, PubMed:12777626, PubMed:24055001, PubMed:23229545, PubMed:26149463). Also catalyzes the transamination between L-serine and pyruvate and contributes to gluconeogenesis from the L-serine metabolism (PubMed:10347152).<ref>PMID:10347152</ref> <ref>PMID:10960483</ref> <ref>PMID:12777626</ref> <ref>PMID:23229545</ref> <ref>PMID:24055001</ref> <ref>PMID:26149463</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alanine:glyoxylate aminotransferase (AGT), a hepatocyte-specific pyridoxal-5'-phosphate (PLP) dependent enzyme, transaminates L-alanine and glyoxylate to glycine and pyruvate, thus detoxifying glyoxylate and preventing pathological oxalate precipitation in tissues. In the widely accepted catalytic mechanism of the aminotransferase family, the lysine binding to PLP acts as a catalyst in the stepwise 1,3-proton transfer, interconverting the external aldimine to ketimine. This step requires protonation by a conserved aspartate of the pyridine nitrogen of PLP to enhance its ability to stabilize the carbanionic intermediate. The aspartate residue is also responsible for a significant geometrical distortion of the internal aldimine, crucial for catalysis. We present the structure of human AGT in which complete X-ray photoreduction of the Schiff base has occurred. This result, together with two crystal structures of the conserved aspartate pathogenic variant (D183N) and the molecular modeling of the transaldimination step, led us to propose that an interplay of opposite forces, which we named spring mechanism, finely tunes PLP geometry during catalysis and is essential to move the external aldimine in the correct position in order for the 1,3-proton transfer to occur. | |||
Radiation damage at the active site of human alanine:glyoxylate aminotransferase reveals that the cofactor position is finely tuned during catalysis.,Giardina G, Paiardini A, Montioli R, Cellini B, Voltattorni CB, Cutruzzola F Sci Rep. 2017 Sep 15;7(1):11704. doi: 10.1038/s41598-017-11948-w. PMID:28916765<ref>PMID:28916765</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Borri Voltattorni | <div class="pdbe-citations 5luc" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Aminotransferase 3D structures|Aminotransferase 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Borri Voltattorni C]] | |||
[[Category: Cellini B]] | |||
[[Category: Cutruzzola F]] | |||
[[Category: Giardina G]] | |||
[[Category: Montioli R]] | |||
Latest revision as of 21:49, 18 October 2023
Crystal structure of the D183N variant of human Alanine:Glyoxylate Aminotransferase major allele (AGT-Ma) at 1.8 Angstrom; internal aldimine with PLP in the active siteCrystal structure of the D183N variant of human Alanine:Glyoxylate Aminotransferase major allele (AGT-Ma) at 1.8 Angstrom; internal aldimine with PLP in the active site
Structural highlights
DiseaseAGT1_HUMAN Primary hyperoxaluria type 1. The disease is caused by variants affecting the gene represented in this entry. FunctionAGT1_HUMAN Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification (PubMed:10960483, PubMed:12777626, PubMed:24055001, PubMed:23229545, PubMed:26149463). Also catalyzes the transamination between L-serine and pyruvate and contributes to gluconeogenesis from the L-serine metabolism (PubMed:10347152).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe alanine:glyoxylate aminotransferase (AGT), a hepatocyte-specific pyridoxal-5'-phosphate (PLP) dependent enzyme, transaminates L-alanine and glyoxylate to glycine and pyruvate, thus detoxifying glyoxylate and preventing pathological oxalate precipitation in tissues. In the widely accepted catalytic mechanism of the aminotransferase family, the lysine binding to PLP acts as a catalyst in the stepwise 1,3-proton transfer, interconverting the external aldimine to ketimine. This step requires protonation by a conserved aspartate of the pyridine nitrogen of PLP to enhance its ability to stabilize the carbanionic intermediate. The aspartate residue is also responsible for a significant geometrical distortion of the internal aldimine, crucial for catalysis. We present the structure of human AGT in which complete X-ray photoreduction of the Schiff base has occurred. This result, together with two crystal structures of the conserved aspartate pathogenic variant (D183N) and the molecular modeling of the transaldimination step, led us to propose that an interplay of opposite forces, which we named spring mechanism, finely tunes PLP geometry during catalysis and is essential to move the external aldimine in the correct position in order for the 1,3-proton transfer to occur. Radiation damage at the active site of human alanine:glyoxylate aminotransferase reveals that the cofactor position is finely tuned during catalysis.,Giardina G, Paiardini A, Montioli R, Cellini B, Voltattorni CB, Cutruzzola F Sci Rep. 2017 Sep 15;7(1):11704. doi: 10.1038/s41598-017-11948-w. PMID:28916765[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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