6ufp: Difference between revisions
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<StructureSection load='6ufp' size='340' side='right'caption='[[6ufp]], [[Resolution|resolution]] 1.74Å' scene=''> | <StructureSection load='6ufp' size='340' side='right'caption='[[6ufp]], [[Resolution|resolution]] 1.74Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ufp]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6ufp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sinorhizobium_meliloti_SM11 Sinorhizobium meliloti SM11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UFP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T2C:(2S)-1,3-thiazolidine-2-carboxylic+acid'>T2C</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.737Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T2C:(2S)-1,3-thiazolidine-2-carboxylic+acid'>T2C</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=6ufp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufp OCA], [https://pdbe.org/6ufp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ufp RCSB], [https://www.ebi.ac.uk/pdbsum/6ufp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufp ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/F7X6I3_SINMM F7X6I3_SINMM] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6ufp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6ufp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Proline utilization A|Proline utilization A]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Sinorhizobium meliloti SM11]] | ||
[[Category: Campbell | [[Category: Campbell AC]] | ||
[[Category: Tanner | [[Category: Tanner JJ]] | ||
Latest revision as of 10:50, 11 October 2023
Structure of proline utilization A with the FAD covalently modified by L-thiazolidine-2-carboxylate and three cysteines (Cys46, Cys470, Cys638) modified to S,S-(2-HYDROXYETHYL)THIOCYSTEINEStructure of proline utilization A with the FAD covalently modified by L-thiazolidine-2-carboxylate and three cysteines (Cys46, Cys470, Cys638) modified to S,S-(2-HYDROXYETHYL)THIOCYSTEINE
Structural highlights
FunctionF7X6I3_SINMM Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197] Publication Abstract from PubMedProline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the FAD-dependent 2-electron oxidation of L-proline to 1-pyrroline-5-carboxylate. PRODH has emerged as a possible cancer therapy target, and thus the inhibition of PRODH is of interest. Here we show that the proline analog thiazolidine-2-carboxylate (T2C) is a mechanism-based inactivator of PRODH. Structures of the bifunctional proline catabol-ic enzyme proline utilization A (PutA) determined from crystals grown in the presence of T2C feature strong electron density for a 5-membered ring species resembling L-T2C covalently bound to the N5 of the FAD in the PRODH domain. The modified FAD exhibits a large butterfly bend angle, indicating that the FAD is locked into the 2-electron reduced state. Reduction of the FAD is consistent with the crystals lacking the distinctive yellow color of the oxidized enzyme and stopped-flow kinetic data showing that T2C is a sub-strate for the PRODH domain of PutA. A mechanism is proposed in which PRODH catalyzes the oxidation of T2C at the C atom adjacent to the S atom of the thiazolidine ring (C5). Then, the N5 atom of the reduced FAD attacks the C5 of the oxidized T2C species, resulting in the covalent adduct observed in the crystal structure. To our knowledge, this is the first report of T2C inactivating (or inhibiting) PRODH or any other flavoenzyme. These results may inform the design of new mechanism-based inactivators of PRODH for use as chemical probes to study the roles of proline metabolism in cancer. Covalent Modification of the Flavin in Proline Dehydrogenase by Thiazolidine-2-Carboxylate.,Campbell AC, Becker DF, Gates KS, Tanner JJ ACS Chem Biol. 2020 Mar 11. doi: 10.1021/acschembio.9b00935. PMID:32159324[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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