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| | ==Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase== | | ==Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase== |
| - | <StructureSection load='3ntj' size='340' side='right' caption='[[3ntj]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='3ntj' size='340' side='right'caption='[[3ntj]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ntj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NTJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NTJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ntj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NTJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lgo|3lgo]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OAT, PFF0435w ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=3ntj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ntj OCA], [https://pdbe.org/3ntj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ntj RCSB], [https://www.ebi.ac.uk/pdbsum/3ntj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ntj 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/Ornithine_aminotransferase Ornithine aminotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.13 2.6.1.13] </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=3ntj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ntj OCA], [http://pdbe.org/3ntj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ntj RCSB], [http://www.ebi.ac.uk/pdbsum/3ntj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ntj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OAT_PLAF7 OAT_PLAF7]] The enzyme has a very narrow substrate specificity and can only catalyze the transamination of alpha-ketoglutarate with ornithine or N-acetylornithine and of glutamate-5-semialdehyde with glutamate and alanine. | + | [https://www.uniprot.org/uniprot/OAT_PLAF7 OAT_PLAF7] The enzyme has a very narrow substrate specificity and can only catalyze the transamination of alpha-ketoglutarate with ornithine or N-acetylornithine and of glutamate-5-semialdehyde with glutamate and alanine. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ornithine aminotransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Becker, K]] | + | [[Category: Becker K]] |
| - | [[Category: Fritz-Wolf, K]] | + | [[Category: Fritz-Wolf K]] |
| - | [[Category: Jortzik, E]] | + | [[Category: Jortzik E]] |
| - | [[Category: Stumpf, M]] | + | [[Category: Stumpf M]] |
| - | [[Category: Alpha-ketoglutarate]]
| + | |
| - | [[Category: Aminotransferase]]
| + | |
| - | [[Category: Ornithine]]
| + | |
| - | [[Category: Plp-dependent enzyme]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
OAT_PLAF7 The enzyme has a very narrow substrate specificity and can only catalyze the transamination of alpha-ketoglutarate with ornithine or N-acetylornithine and of glutamate-5-semialdehyde with glutamate and alanine.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ornithine delta-aminotransferase (OAT) of the malaria parasite Plasmodium falciparum catalyzes the reversible conversion of ornithine into glutamate-5-semialdehyde and glutamate and is-in contrast to its human counterpart-activated by thioredoxin (Trx) by a factor of 10. Trx, glutaredoxin, and plasmoredoxin are redox-active proteins that play a crucial role in the maintenance and control of redox reactions, and were shown to interact with P. falciparum OAT. OAT, which is involved in ornithine homeostasis and proline biosynthesis, is essential for mitotic cell division in rapidly growing cells, thus representing a potential target for chemotherapeutic intervention. Here we report the three-dimensional crystal structure of P. falciparum OAT at 2.3 A resolution. The overall structure is very similar to that of the human OAT. However, in plasmodial OAT, the loop involved in substrate binding contains two cysteine residues, which are lacking in human OAT. Site-directed mutagenesis of these cysteines and functional analysis demonstrated that Cys154 and Cys163 mediate the interaction with Trx. Interestingly, the Cys154-->Ser mutant has a strongly reduced specific activity, most likely due to impaired binding of ornithine. Cys154 and Cys163 are highly conserved in Plasmodium but do not exist in other organisms, suggesting that redox regulation of OAT by Trx is specific for malaria parasites. Plasmodium might require a tight Trx-mediated control of OAT activity for coordinating ornithine homeostasis, polyamine synthesis, proline synthesis, and mitotic cell division.
Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase.,Jortzik E, Fritz-Wolf K, Sturm N, Hipp M, Rahlfs S, Becker K J Mol Biol. 2010 Sep 17;402(2):445-59. Epub 2010 Jul 29. PMID:20673832[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jortzik E, Fritz-Wolf K, Sturm N, Hipp M, Rahlfs S, Becker K. Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase. J Mol Biol. 2010 Sep 17;402(2):445-59. Epub 2010 Jul 29. PMID:20673832 doi:10.1016/j.jmb.2010.07.039
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