8apq
From Proteopedia
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<table><tr><td colspan='2'>[[8apq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Chloroflexus_aurantiacus_J-10-fl Chloroflexus aurantiacus J-10-fl]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8APQ FirstGlance]. <br> | <table><tr><td colspan='2'>[[8apq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Chloroflexus_aurantiacus_J-10-fl Chloroflexus aurantiacus J-10-fl]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8APQ 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]] 2.49Å</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]] 2.49Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MEZ:(2E)-2-METHYLBUT-2-ENEDIOIC+ACID'>MEZ</scene>, <scene name='pdbligand=OA9: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MEZ:(2E)-2-METHYLBUT-2-ENEDIOIC+ACID'>MEZ</scene>, <scene name='pdbligand=OA9:(~{E})-4-[2-[3-[[(2~{R})-4-[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-3,3-dimethyl-2-oxidanyl-butanoyl]amino]propanoylamino]ethylsulfanyl]-3-methyl-4-oxidanylidene-but-2-enoic+acid'>OA9</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=8apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8apq OCA], [https://pdbe.org/8apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8apq RCSB], [https://www.ebi.ac.uk/pdbsum/8apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8apq 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=8apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8apq OCA], [https://pdbe.org/8apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8apq RCSB], [https://www.ebi.ac.uk/pdbsum/8apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8apq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Mesaconyl-CoA transferase (Mct) is one of the key enzymes of the 3-hydroxypropionate (3HP) bi-cycle for autotrophic CO(2) fixation. Mct is a family III/Frc family CoA transferase that catalyzes an unprecedented intra-molecular CoA transfer from the C1-carboxyl group to the C4-carboxyl group of mesaconate at catalytic efficiencies >10(6) M(-1) s(-1). Here, we show that the reaction of Mct proceeds without any significant release of free CoA or the transfer to external acceptor acids. Mct catalyzes intra-molecular CoA transfers at catalytic efficiencies that are at least more than 6 orders of magnitude higher compared to inter-molecular CoA transfers, demonstrating that the enzyme exhibits exquisite control over its reaction. To understand the molecular basis of the intra-molecular CoA transfer in Mct, we solved crystal structures of the enzyme from Chloroflexus aurantiacus in its apo form, as well as in complex with mesaconyl-CoA and several covalently enzyme-bound intermediates of CoA and mesaconate at the catalytically active residue Asp165. Based on these structures, we propose a reaction mechanism for Mct that is similar to inter-molecular family III/Frc family CoA transferases. However, in contrast to the latter that undergo opening and closing cycles during the reaction to exchange substrates, the central cavity of Mct remains sealed ("corked-up") by the CoA moiety, strongly favoring the intra-molecular CoA transfer between the C1 and the C4 position of mesaconate. | Mesaconyl-CoA transferase (Mct) is one of the key enzymes of the 3-hydroxypropionate (3HP) bi-cycle for autotrophic CO(2) fixation. Mct is a family III/Frc family CoA transferase that catalyzes an unprecedented intra-molecular CoA transfer from the C1-carboxyl group to the C4-carboxyl group of mesaconate at catalytic efficiencies >10(6) M(-1) s(-1). Here, we show that the reaction of Mct proceeds without any significant release of free CoA or the transfer to external acceptor acids. Mct catalyzes intra-molecular CoA transfers at catalytic efficiencies that are at least more than 6 orders of magnitude higher compared to inter-molecular CoA transfers, demonstrating that the enzyme exhibits exquisite control over its reaction. To understand the molecular basis of the intra-molecular CoA transfer in Mct, we solved crystal structures of the enzyme from Chloroflexus aurantiacus in its apo form, as well as in complex with mesaconyl-CoA and several covalently enzyme-bound intermediates of CoA and mesaconate at the catalytically active residue Asp165. Based on these structures, we propose a reaction mechanism for Mct that is similar to inter-molecular family III/Frc family CoA transferases. However, in contrast to the latter that undergo opening and closing cycles during the reaction to exchange substrates, the central cavity of Mct remains sealed ("corked-up") by the CoA moiety, strongly favoring the intra-molecular CoA transfer between the C1 and the C4 position of mesaconate. | ||
| - | Structural Basis for a Cork-Up Mechanism of the Intra-Molecular Mesaconyl-CoA Transferase.,Pfister P, Zarzycki J, Erb TJ Biochemistry. | + | Structural Basis for a Cork-Up Mechanism of the Intra-Molecular Mesaconyl-CoA Transferase.,Pfister P, Zarzycki J, Erb TJ Biochemistry. 2023 Jan 3;62(1):75-84. doi: 10.1021/acs.biochem.2c00532. Epub 2022 , Dec 19. PMID:36535006<ref>PMID:36535006</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
CaMct - Mesaconyl-CoA C1:C4 CoA Transferase of Chloroflexus aurantiacus
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