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3v9k

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==Crystal structure of mouse 1-pyrroline-5-carboxylate dehydrogenase complexed with the product glutamate==
==Crystal structure of mouse 1-pyrroline-5-carboxylate dehydrogenase complexed with the product glutamate==
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<StructureSection load='3v9k' size='340' side='right' caption='[[3v9k]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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<StructureSection load='3v9k' size='340' side='right'caption='[[3v9k]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3v9k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V9K FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3v9k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V9K FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.501&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v9g|3v9g]], [[3v9h|3v9h]], [[3v9i|3v9i]], [[3v9j|3v9j]], [[3v9l|3v9l]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Aldh4a1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v9k OCA], [https://pdbe.org/3v9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v9k RCSB], [https://www.ebi.ac.uk/pdbsum/3v9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v9k ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-pyrroline-5-carboxylate_dehydrogenase 1-pyrroline-5-carboxylate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.12 1.5.1.12] </span></td></tr>
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<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=3v9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v9k RCSB], [http://www.ebi.ac.uk/pdbsum/3v9k PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/AL4A1_MOUSE AL4A1_MOUSE] Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes (By similarity).
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Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-A-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 A) and S352L (2.85 A) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 A resolution), glutamate (1.5 A), and NAD(+) (1.5 A) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD(+) binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-A rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD(+), and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.
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The Three-Dimensional Structural Basis of Type II Hyperprolinemia.,Srivastava D, Singh RK, Moxley MA, Henzl MT, Becker DF, Tanner JJ J Mol Biol. 2012 Apr 16. PMID:22516612<ref>PMID:22516612</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
*[[Pyrroline-5-carboxylate dehydrogenase|Pyrroline-5-carboxylate dehydrogenase]]
*[[Pyrroline-5-carboxylate dehydrogenase|Pyrroline-5-carboxylate dehydrogenase]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: 1-pyrroline-5-carboxylate dehydrogenase]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Srivastava, D]]
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[[Category: Srivastava D]]
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[[Category: Tanner, J J]]
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[[Category: Tanner JJ]]
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[[Category: Acting on aldehyde or oxo group of donor]]
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[[Category: Aldehyde dehydrogenase]]
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[[Category: Mitochondria]]
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[[Category: Nad or nadp as acceptor]]
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[[Category: Nucleotide binding]]
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[[Category: Oxidoreductase]]
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[[Category: Rossmann fold]]
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Current revision

Crystal structure of mouse 1-pyrroline-5-carboxylate dehydrogenase complexed with the product glutamate

PDB ID 3v9k

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