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| | <StructureSection load='2ekg' size='340' side='right'caption='[[2ekg]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2ekg' size='340' side='right'caption='[[2ekg]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ekg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thet2 Thet2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EKG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ekg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB27 Thermus thermophilus HB27]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EKG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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]] 1.9Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYX:N-(2-COENZYME+A)-PROPANOYL-LYSINE'>LYX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=LYX:N-(2-COENZYME+A)-PROPANOYL-LYSINE'>LYX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2g37|2g37]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PROLINE DEHYDROGENASE/DELTA-1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=262724 THET2])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Proline_dehydrogenase Proline dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.99.8 1.5.99.8] </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=2ekg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ekg OCA], [https://pdbe.org/2ekg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ekg RCSB], [https://www.ebi.ac.uk/pdbsum/2ekg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ekg ProSAT]</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=2ekg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ekg OCA], [https://pdbe.org/2ekg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ekg RCSB], [https://www.ebi.ac.uk/pdbsum/2ekg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ekg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PRODH_THET2 PRODH_THET2] Converts proline to delta-1-pyrroline-5-carboxylate (PubMed:17344208, PubMed:18426222). Has significant activity against O(2) producing superoxide during proline oxidation catalytic cycle (PubMed:17344208).<ref>PMID:17344208</ref> <ref>PMID:18426222</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Proline dehydrogenase]] | + | [[Category: Thermus thermophilus HB27]] |
| - | [[Category: Thet2]]
| + | [[Category: Tanner JJ]] |
| - | [[Category: Tanner, J J]] | + | [[Category: White TA]] |
| - | [[Category: White, T A]] | + | |
| - | [[Category: Beta-alpha-barrel]]
| + | |
| - | [[Category: Flavocyanine]]
| + | |
| - | [[Category: Flavoenzyme]]
| + | |
| - | [[Category: Inactivation]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Prodh]]
| + | |
| - | [[Category: Suicide inhibitor]]
| + | |
| Structural highlights
Function
PRODH_THET2 Converts proline to delta-1-pyrroline-5-carboxylate (PubMed:17344208, PubMed:18426222). Has significant activity against O(2) producing superoxide during proline oxidation catalytic cycle (PubMed:17344208).[1] [2]
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
The flavoenzyme proline dehydrogenase catalyzes the first step of proline catabolism, the oxidation of proline to pyrroline-5-carboxylate. Here we report the first crystal structure of an irreversibly inactivated proline dehydrogenase. The 1.9 A resolution structure of Thermus thermophilus proline dehydrogenase inactivated by the mechanism-based inhibitor N-propargylglycine shows that N5 of the flavin cofactor is covalently connected to the -amino group of Lys99 via a three-carbon linkage, consistent with the mass spectral analysis of the inactivated enzyme. The isoalloxazine ring has a butterfly angle of 25 degrees , which suggests that the flavin cofactor is reduced. Two mechanisms can account for these observations. In both, N-propargylglycine is oxidized to N-propargyliminoglycine. In one mechanism, this alpha,beta-unsaturated iminium compound is attacked by the N5 atom of the now reduced flavin to produce a 1,4-addition product. Schiff base formation between Lys99 and the imine of the 1,4-addition product releases glycine and links the enzyme to the modified flavin. In the second mechanism, hydrolysis of N-propargyliminoglycine yields propynal and glycine. A 1,4-addition reaction with propynal coupled with Schiff base formation between Lys99 and the carbonyl group tethers the enzyme to the flavin via a three-carbon chain. The presumed nonenzymatic hydrolysis of N-propargyliminoglycine and the subsequent rebinding of propynal to the enzyme make the latter mechanism less likely.
Structural basis for the inactivation of Thermus thermophilus proline dehydrogenase by N-propargylglycine.,White TA, Johnson WH Jr, Whitman CP, Tanner JJ Biochemistry. 2008 May 20;47(20):5573-80. Epub 2008 Apr 22. PMID:18426222[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ White TA, Krishnan N, Becker DF, Tanner JJ. Structure and kinetics of monofunctional proline dehydrogenase from Thermus thermophilus. J Biol Chem. 2007 May 11;282(19):14316-27. Epub 2007 Mar 7. PMID:17344208 doi:10.1074/jbc.M700912200
- ↑ White TA, Johnson WH Jr, Whitman CP, Tanner JJ. Structural basis for the inactivation of Thermus thermophilus proline dehydrogenase by N-propargylglycine. Biochemistry. 2008 May 20;47(20):5573-80. Epub 2008 Apr 22. PMID:18426222 doi:10.1021/bi800055w
- ↑ White TA, Johnson WH Jr, Whitman CP, Tanner JJ. Structural basis for the inactivation of Thermus thermophilus proline dehydrogenase by N-propargylglycine. Biochemistry. 2008 May 20;47(20):5573-80. Epub 2008 Apr 22. PMID:18426222 doi:10.1021/bi800055w
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