5luc: Difference between revisions

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<StructureSection load='5luc' size='340' side='right'caption='[[5luc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='5luc' size='340' side='right'caption='[[5luc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5luc]] is a 8 chain structure. 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 [http://proteopedia.org/fgij/fg.htm?mol=5LUC FirstGlance]. <br>
<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='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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f9s|5f9s]], [[5hhy|5hhy]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine--pyruvate_transaminase Serine--pyruvate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.51 2.6.1.51] </span></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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5luc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5luc OCA], [http://pdbe.org/5luc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5luc RCSB], [http://www.ebi.ac.uk/pdbsum/5luc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5luc ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/SPYA_HUMAN SPYA_HUMAN]] Defects in AGXT are the cause of hyperoxaluria primary type 1 (HP1) [MIM:[http://omim.org/entry/259900 259900]]; also known as primary hyperoxaluria type I (PH1) and oxalosis I. HP1 is a rare autosomal recessive inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and the progressive accumulation of insoluble calcium oxalate in the kidney and urinary tract.<ref>PMID:1703535</ref> <ref>PMID:2039493</ref> <ref>PMID:1349575</ref> <ref>PMID:1301173</ref> <ref>PMID:8101040</ref> <ref>PMID:9192270</ref> <ref>PMID:9604803</ref> <ref>PMID:10394939</ref> <ref>PMID:10453743</ref> <ref>PMID:10541294</ref> <ref>PMID:10862087</ref> <ref>PMID:10960483</ref> <ref>PMID:12559847</ref> <ref>PMID:12777626</ref> <ref>PMID:15253729</ref> <ref>PMID:15849466</ref> <ref>PMID:15961946</ref> <ref>PMID:15963748</ref>
[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;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Serine--pyruvate transaminase]]
[[Category: Borri Voltattorni C]]
[[Category: Cellini, B]]
[[Category: Cellini B]]
[[Category: Cutruzzola, F]]
[[Category: Cutruzzola F]]
[[Category: Giardina, G]]
[[Category: Giardina G]]
[[Category: Montioli, R]]
[[Category: Montioli R]]
[[Category: Voltattorni, C Borri]]
[[Category: Ph1]]
[[Category: Primary hyperoxaluria type i]]
[[Category: Transferase]]

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

5luc is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AGT1_HUMAN Primary hyperoxaluria type 1. The disease is caused by variants affecting the gene represented in this entry.

Function

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).[1] [2] [3] [4] [5] [6]

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[7]

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

See Also

References

  1. ↑ Xue HH, Sakaguchi T, Fujie M, Ogawa H, Ichiyama A. Flux of the L-serine metabolism in rabbit, human, and dog livers. Substantial contributions of both mitochondrial and peroxisomal serine:pyruvate/alanine:glyoxylate aminotransferase. J Biol Chem. 1999 Jun 4;274(23):16028-33. doi: 10.1074/jbc.274.23.16028. PMID:10347152 doi:http://dx.doi.org/10.1074/jbc.274.23.16028
  2. ↑ Lumb MJ, Danpure CJ. Functional synergism between the most common polymorphism in human alanine:glyoxylate aminotransferase and four of the most common disease-causing mutations. J Biol Chem. 2000 Nov 17;275(46):36415-22. PMID:10960483 doi:10.1074/jbc.M006693200
  3. ↑ Santana A, Salido E, Torres A, Shapiro LJ. Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase. Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7277-82. Epub 2003 May 30. PMID:12777626 doi:10.1073/pnas.1131968100
  4. ↑ Fargue S, Lewin J, Rumsby G, Danpure CJ. Four of the most common mutations in primary hyperoxaluria type 1 unmask the cryptic mitochondrial targeting sequence of alanine:glyoxylate aminotransferase encoded by the polymorphic minor allele. J Biol Chem. 2013 Jan 25;288(4):2475-84. doi: 10.1074/jbc.M112.432617. Epub 2012 , Dec 10. PMID:23229545 doi:http://dx.doi.org/10.1074/jbc.M112.432617
  5. ↑ Oppici E, Roncador A, Montioli R, Bianconi S, Cellini B. Gly161 mutations associated with Primary Hyperoxaluria Type I induce the cytosolic aggregation and the intracellular degradation of the apo-form of alanine:glyoxylate aminotransferase. Biochim Biophys Acta. 2013 Dec;1832(12):2277-88. doi:, 10.1016/j.bbadis.2013.09.002. Epub 2013 Sep 17. PMID:24055001 doi:http://dx.doi.org/10.1016/j.bbadis.2013.09.002
  6. ↑ Montioli R, Oppici E, Dindo M, Roncador A, Gotte G, Cellini B, Borri Voltattorni C. Misfolding caused by the pathogenic mutation G47R on the minor allele of alanine:glyoxylate aminotransferase and chaperoning activity of pyridoxine. Biochim Biophys Acta. 2015 Oct;1854(10 Pt A):1280-9. doi:, 10.1016/j.bbapap.2015.07.002. Epub 2015 Jul 3. PMID:26149463 doi:http://dx.doi.org/10.1016/j.bbapap.2015.07.002
  7. ↑ Giardina G, Paiardini A, Montioli R, Cellini B, Voltattorni CB, Cutruzzola F. Radiation damage at the active site of human alanine:glyoxylate aminotransferase reveals that the cofactor position is finely tuned during catalysis. Sci Rep. 2017 Sep 15;7(1):11704. doi: 10.1038/s41598-017-11948-w. PMID:28916765 doi:http://dx.doi.org/10.1038/s41598-017-11948-w

5luc, resolution 1.80Å

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