8uq0
From Proteopedia
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(New page: '''Unreleased structure''' The entry 8uq0 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Minimal PutA proline dehydrogenase domain (design #2) complexed with 2-(Cyanomethylthio)acetic acid== | |
| + | <StructureSection load='8uq0' size='340' side='right'caption='[[8uq0]], [[Resolution|resolution]] 1.43Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8uq0]] 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=8UQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UQ0 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43Å</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=X7K:[(cyanomethyl)sulfanyl]acetic+acid'>X7K</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=8uq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uq0 OCA], [https://pdbe.org/8uq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uq0 RCSB], [https://www.ebi.ac.uk/pdbsum/8uq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uq0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The flavoenzyme proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the oxidation of l-proline to Delta(1)-pyrroline-5-carboxylate. The enzyme is a target for chemical probe discovery because of its role in the metabolism of certain cancer cells. N-propargylglycine is the first and best characterized mechanism-based covalent inactivator of PRODH. This compound consists of a recognition module (glycine) that directs the inactivator to the active site and an alkyne warhead that reacts with the FAD after oxidative activation, leading to covalent modification of the FAD N5 atom. Here we report structural and kinetic data on analogs of N-propargylglycine with the goals of understanding the initial docking step of the inactivation mechanism and to test the allyl group as a warhead. The crystal structures of PRODH complexed with unreactive analogs in which N is replaced by S show how the recognition module mimics the substrate proline by forming ion pairs with conserved arginine and lysine residues. Further, the C atom adjacent to the alkyne warhead is optimally positioned for hydride transfer to the FAD, providing the structural basis for the first bond-breaking step of the inactivation mechanism. The structures also suggest new strategies for designing improved N-propargylglycine analogs. N-allylglycine, which consists of a glycine recognition module and allyl warhead, is shown to be a covalent inactivator; however, it is less efficient than N-propargylglycine in both enzyme inactivation and cellular assays. Crystal structures of the N-allylglycine-inactivated enzyme are consistent with covalent modification of the N5 by propanal. | ||
| - | + | Noncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs of N-Propargylglycine.,Tanner JJ, Ji J, Bogner AN, Scott GK, Patel SM, Seravalli J, Gates KS, Benz CC, Becker DF Biochemistry. 2024 Oct 22. doi: 10.1021/acs.biochem.4c00429. PMID:39437336<ref>PMID:39437336</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8uq0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Sinorhizobium meliloti SM11]] | ||
| + | [[Category: Tanner JJ]] | ||
Current revision
Minimal PutA proline dehydrogenase domain (design #2) complexed with 2-(Cyanomethylthio)acetic acid
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