7myc: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='7myc' size='340' side='right'caption='[[7myc]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='7myc' size='340' side='right'caption='[[7myc]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7myc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYC FirstGlance]. <br> | <table><tr><td colspan='2'>[[7myc]] 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=7MYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UJG:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-5-[(2R)-tetrahydrothiophen-2-yl]-1,3,4,5-tetrahydrobenzo[g]pteridin-10(2H)-yl}-2,3,4-trihydroxypentyl+dihydrogen+diphosphate+(non-preferred+name)'>UJG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UJG:[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-5-[(2R)-tetrahydrothiophen-2-yl]-1,3,4,5-tetrahydrobenzo[g]pteridin-10(2H)-yl}-2,3,4-trihydroxypentyl+dihydrogen+diphosphate+(non-preferred+name)'>UJG</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=7myc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myc OCA], [https://pdbe.org/7myc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myc RCSB], [https://www.ebi.ac.uk/pdbsum/7myc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myc 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=7myc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myc OCA], [https://pdbe.org/7myc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myc RCSB], [https://www.ebi.ac.uk/pdbsum/7myc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myc ProSAT]</span></td></tr> | ||
</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] | [[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 == | ||
| Line 26: | Line 26: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Sinorhizobium meliloti SM11]] | ||
[[Category: | [[Category: Campbell AC]] | ||
[[Category: | [[Category: Tanner JJ]] | ||
Revision as of 06:49, 8 September 2022
Structure of proline utilization A with the FAD covalently modified by tetrahydrothiopheneStructure of proline utilization A with the FAD covalently modified by tetrahydrothiophene
Structural highlights
Function[F7X6I3_SINMM] Oxidizes proline to glutamate for use as a carbon and nitrogen source.[PIRNR:PIRNR000197] Publication Abstract from PubMedProline dehydrogenase (PRODH) is a flavoenzyme that catalyzes the first step of proline catabolism, the oxidation of l-proline to Delta(1)-pyrroline-5-carboxylate. PRODH has emerged as a cancer therapy target because of its involvement in the metabolic reprogramming of cancer cells. Here, we report the discovery of a new class of PRODH inactivator, which covalently and irreversibly modifies the FAD in a light-dependent manner. Two examples, 1,3-dithiolane-2-carboxylate and tetrahydrothiophene-2-carboxylate, have been characterized using X-ray crystallography (1.52-1.85 A resolution), absorbance spectroscopy, and enzyme kinetics. The structures reveal that in the dark, these compounds function as classical reversible, proline analogue inhibitors. However, exposure of enzyme-inhibitor cocrystals to bright white light induces decarboxylation of the inhibitor and covalent attachment of the residual S-heterocycle to the FAD N5 atom, locking the cofactor into a reduced, inactive state. Spectroscopic measurements of the inactivation process in solution confirm the requirement for light and show that blue light is preferred. Enzyme activity assays show that the rate of inactivation is enhanced by light and that the inactivation is irreversible. We also demonstrate the photosensitivity of cancer cells to one of these compounds. A possible mechanism is proposed involving photoexcitation of the FAD, while the inhibitor is noncovalently bound in the active site, followed by electron transfer, decarboxylation, and radical combination steps. Our results could lead to the development of photopharmacological drugs targeting PRODH. Photoinduced Covalent Irreversible Inactivation of Proline Dehydrogenase by S-Heterocycles.,Campbell AC, Prater AR, Bogner AN, Quinn TP, Gates KS, Becker DF, Tanner JJ ACS Chem Biol. 2021 Sep 20. doi: 10.1021/acschembio.1c00427. PMID:34542291[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||