1h0c: Difference between revisions

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-[[Image:1h0c.gif|left|200px]]<br />
-<applet load="1h0c" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1h0c, resolution 2.50&Aring;" />
-'''THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE'''<br />
-==Overview==
+==The crystal structure of human alanine:glyoxylate aminotransferase==
-A deficiency of the liver-specific enzyme alanine:glyoxylate, aminotransferase (AGT) is responsible for the potentially lethal, hereditary kidney stone disease primary hyperoxaluria type 1 (PH1). Many, of the mutations in the gene encoding AGT are associated with specific, enzymatic phenotypes such as accelerated proteolysis (Ser205Pro), intra-peroxisomal aggregation (Gly41Arg), inhibition of pyridoxal, phosphate binding and loss of catalytic activity (Gly82Glu), and, peroxisome-to-mitochondrion mistargeting (Gly170Arg). Several mutations, including that responsible for AGT mistargeting, co-segregate and interact, synergistically with a Pro11Leu polymorphism found at high frequency in, the normal population. In order to gain further insights into the, mechanistic link between genotype and enzymatic phenotype in PH1, we have, determined the crystal structure of normal human AGT complexed to the, competitive inhibitor amino-oxyacetic acid to 2.5A. Analysis of this, structure allows the effects of these mutations and polymorphism to be, rationalised in terms of AGT tertiary and quaternary conformation, and in, particular it provides a possible explanation for the Pro11Leu-Gly170Arg, synergism that leads to AGT mistargeting.
+<StructureSection load='1h0c' size='340' side='right'caption='[[1h0c]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1h0c]] 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=1H0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H0C 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]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AOA:(AMINOOXY)ACETIC+ACID'>AOA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=1h0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0c OCA], [https://pdbe.org/1h0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h0c RCSB], [https://www.ebi.ac.uk/pdbsum/1h0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h0c 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/1h0c_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h0c ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-Known diseases associated with this structure: Hyperoxaluria, primary, type 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604285 604285]]
+*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-H0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PLP, AOA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H0C OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1., Zhang X, Roe SM, Hou Y, Bartlam M, Rao Z, Pearl LH, Danpure CJ, J Mol Biol. 2003 Aug 15;331(3):643-52. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12899834 12899834]
-[[Category: Alanine--glyoxylate transaminase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Danpure, C.J.]]
+[[Category: Danpure CJ]]
-[[Category: Pearl, L.H.]]
+[[Category: Pearl LH]]
-[[Category: Roe, S.M.]]
+[[Category: Roe SM]]
-[[Category: Zhang, X.]]
+[[Category: Zhang X]]
-[[Category: AOA]]
-[[Category: GOL]]
-[[Category: PLP]]
-[[Category: aminotransferase]]
-[[Category: pyridoxal phosphate]]
-[[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:11:08 2007''