4cbr: Difference between revisions

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<StructureSection load='4cbr' size='340' side='right'caption='[[4cbr]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='4cbr' size='340' side='right'caption='[[4cbr]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4cbr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CBR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CBR FirstGlance]. <br>
<table><tr><td colspan='2'>[[4cbr]] is a 1 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=4CBR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CBR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
</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>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cbs|4cbs]]</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=4cbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbr OCA], [https://pdbe.org/4cbr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cbr RCSB], [https://www.ebi.ac.uk/pdbsum/4cbr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbr 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/Alanine--glyoxylate_transaminase Alanine--glyoxylate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.44 2.6.1.44] </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=4cbr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cbr OCA], [http://pdbe.org/4cbr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cbr RCSB], [http://www.ebi.ac.uk/pdbsum/4cbr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cbr 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.
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[[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>  
Protein stability is a fundamental issue in biomedical and biotechnological applications of proteins. Among them, gene- and enzyme-replacement strategies are promising approaches to treat inherited diseases that may benefit from protein engineering techniques, even though these beneficial effects have been largely unexplored. We apply here a sequence-alignment statistics procedure (consensus-based approach) to improve the activity and stability of the human alanine:glyoxylate aminotransferase (AGT) protein, an enzyme which causes primary hyperoxaluria type I (PH1) upon mutation. By combining only five consensus mutations, we obtain a variant (AGT-RHEAM) with largely enhanced in vitro thermal and kinetic stability, increased activity and no side effects on foldability and peroxisomal targeting in mammalian cells. The structure of AGT-RHEAM reveals changes at the dimer interface and improved electrostatic interactions responsible for increased kinetic stability. Consensus-based variants maintain the overall protein fold, crystallized more easily and improve the expression as soluble proteins in two different systems (AGT and CIPK24/SOS2). Thus, the consensus-based approach also emerges as a simple and generic strategy to increase the crystallization success for hard-to-get protein targets as well as to enhance protein stability and function for biomedical applications.
 
The consensus-based approach for gene/enzyme replacement therapies and crystallization strategies: the case of human alanine:glyoxylate aminotransferase.,Mesa-Torres N, Yunta C, Fabelo-Rosa I, Gonzalez-Rubio JM, Sanchez-Ruiz JM, Salido E, Albert A, Pey AL Biochem J. 2014 Jun 24. PMID:24957194<ref>PMID:24957194</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cbr" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Alanine--glyoxylate transaminase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Albert, A]]
[[Category: Albert A]]
[[Category: Yunta, C]]
[[Category: Yunta C]]
[[Category: Primary hiperoxaluria type i]]
[[Category: Transferase]]
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