3uqd
From Proteopedia
(Difference between revisions)
| Line 10: | Line 10: | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uqd OCA], [http://pdbe.org/3uqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uqd RCSB], [http://www.ebi.ac.uk/pdbsum/3uqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uqd ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uqd OCA], [http://pdbe.org/3uqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uqd RCSB], [http://www.ebi.ac.uk/pdbsum/3uqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uqd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phosphofructokinases (Pfks) catalyze the ATP-dependent phosphorylation of fructose-6-phosphate (F6P) and they are regulated in a wide variety of organisms. Although numerous aspects of the kinetics and regulation have been characterized for Pfks, the knowledge about the mechanism of the phosphoryl transfer reaction and the transition state lags behind. In this work, we describe the X-ray crystal structure of the homodimeric Pfk-2 from E. coli, which contains products in one site and reactants in the other, as well as an additional ATP molecule in the inhibitory allosteric site adjacent to the reactants. This complex was previously predicted when studying the kinetic mechanism of ATP inhibition. After removing the allosteric ATP, molecular dynamic (MD) simulations revealed conformational changes related to domain packing, as well as stable interactions of Lys27 and Asp256 with donor (ATP) and acceptor (fructose-6-) groups, and of Asp166 with Mg(2+). The phosphoryl transfer reaction mechanism catalyzed by Pfk-2 was investigated through Quantum Mechanics/Molecular Mechanics (QM/MM) simulations using a combination of the string method and a path-collective variable for the exploration of its free energy surface. The calculated activation free energies showed that a dissociative mechanism, occurring with a metaphosphate intermediate formation followed by a proton transfer to Asp256, is more favorable than an associative one. The structural analysis reveals the role of Asp256 acting as a catalytic base and Lys27 stabilizing the transition state of the dissociative mechanism. | ||
| + | |||
| + | Studying the phosphoryl transfer mechanism of the E. coli phosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simulations.,Murillo-Lopez J, Zinovjev K, Pereira H, Caniuguir A, Garratt R, Babul J, Recabarren R, Alzate-Morales J, Caballero J, Tunon I, Cabrera R Chem Sci. 2019 Jan 28;10(10):2882-2892. doi: 10.1039/c9sc00094a. eCollection 2019, Mar 14. PMID:30996866<ref>PMID:30996866</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3uqd" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Phosphofructokinase (PFK)|Phosphofructokinase (PFK)]] | *[[Phosphofructokinase (PFK)|Phosphofructokinase (PFK)]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 11:20, 13 November 2019
Crystal structure of the Phosphofructokinase-2 from Escherichia coli in complex with substrates and products
| |||||||||||
