The substrate reactivity of .mu.-monothiopyrophosphate with pyrophosphate-dependent phosphofructokinase: evidence for a dissociative transition state in enzymic phosphoryl group transfer

Biochemistry ◽  
1991 ◽  
Vol 30 (42) ◽  
pp. 10313-10322 ◽  
Author(s):  
Christopher J. Halkides ◽  
Eric S. Lightcap ◽  
Perry A. Frey
Keyword(s):  
Transition State ◽  
Phosphoryl Group ◽  
Group Transfer ◽  
Substrate Reactivity

Phosphotransfer and Nucleotidyltransfer

2007 ◽  
Author(s):  
Perry A. Frey ◽  
Adrian D. Hegeman
Keyword(s):  
Transition State ◽  
Molecular Mechanisms ◽  
Enzymatic Reaction ◽  
Covalent Bond ◽  
Phosphoryl Group ◽  
Dissociative Mechanism ◽  
Chemical Mechanisms ◽  
Cellular Processes ◽  
Nucleic Acid Biosynthesis ◽  
Transfer Mechanisms

Phosphotransferases, phosphatases, and nucleotidyltransferases catalyze nucleophilic substitution at phosphorus. They constitute a dominant class of enzymes in intermediary metabolism, energy transduction, nucleic acid biosynthesis and processing, and regulation of many cellular processes, including replication, cellular development, and apoptosis. The mechanisms of the action of these enzymes have been studied intensively at several levels, ranging from the biosynthesis of metabolites and nucleic acids to unmasking signaling networks to elucidating the molecular mechanisms of catalysis. We focus on the chemical mechanisms of the reactions of biological phosphates. More than 40 years of research on this chemistry reveals that the mechanisms can be grouped into two classes: the phosphoryl group (PO3−) transfer mechanisms and the nucleotidyl or alkylphosphoryl group (ROPO2−) transfer mechanisms. Because the fundamental chemical mechanisms of these reactions are not treated in textbooks, we begin by considering this chemistry and then move on to the enzymatic reaction mechanisms. Phosphomonoesters, phosphoanhydrides, and phosphoramidates undergo substitution at phosphorus by transfer of the phosphoryl (PO3–) group, that is, by P—O and P—N cleavage. The current description of a typical phosphoryl group transfer mechanism is one in which the phosphoryl donor and acceptor interact weakly with the phosphoryl group in flight in a transition state in which the total bonding to phosphorus is decreased relative to the ground state. The bonding is weak between phosphorus and the leaving group R–X and between phosphorus and the accepting group Y in the transition state of. Because of decreased bonding to phosphorus, this is a loose transition state that has been described as dissociative. The latter should not be confused with the dissociative mechanism, which is considered later. To avoid confusion, we use the term loose transition state. Detailed studies indicate that the bonding denoted by the dashed lines in represents partial covalency on the order of 10% to 20% of the strength of a full covalent bond, or a bond order of 0.1 to 0.2.

scholarly journals Routes of phosphoryl group transfer during signal transmission and signal decay in the dimeric sensor histidine kinase ArcB

2018 ◽  
Vol 293 (34) ◽  
pp. 13214-13223 ◽  
Author(s):  
Juan L. Teran-Melo ◽  
Gabriela R. Peña-Sandoval ◽  
Hortencia Silva-Jimenez ◽  
Claudia Rodriguez ◽  
Adrián F. Alvarez ◽  
...  
Keyword(s):  
Histidine Kinase ◽  
Signal Transmission ◽  
Phosphoryl Group ◽  
Sensor Histidine Kinase ◽  
Group Transfer ◽  
Signal Decay

Mechanism of Phosphoryl Group Transfer

2003 ◽  
Vol 986 (1) ◽  
pp. 275-277 ◽  
Author(s):  
L. D. FALLER ◽  
A. K. NAGY ◽  
D. J. KANE ◽  
R. A. FARLEY
Keyword(s):  
Phosphoryl Group ◽  
Group Transfer

Stereochemistry of phosphoryl group transfer using a chiral [16O, 17O, 18O] stereochemical course of alkaline phosphatase

Nature ◽  
1978 ◽  
Vol 275 (5680) ◽  
pp. 564-565 ◽  
Author(s):  
STEPHEN R. JONES ◽  
L. ALLEN KINDMAN ◽  
JEREMY R. KNOWLES
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphoryl Group ◽  
Group Transfer

scholarly journals An Unprecedented Octahedral Trifluoromagnesate MgF3(Wat)– Transition State Analog Reveals The Molecular Mechanism of ATP Hydrolysis by Zika Virus Helicase

2020 ◽  
Author(s):  
Mengyu Ge ◽  
Robert W. Molt Jr ◽  
Huw T. Jenkins ◽  
G. Michael Blackburn ◽  
Yi Jin ◽  
...  
Keyword(s):  
Transition State ◽  
Zika Virus ◽  
Active Sites ◽  
Atp Hydrolysis ◽  
Structural Data ◽  
Data Interpretation ◽  
Phosphoryl Group ◽  
Metal Fluoride ◽  
Catalytic Core ◽  
Transition State Analog

Metal fluoride complexes mimic the transferring phosphoryl group in many enzyme-catalyzed reactions. We here employ the trifluoromagnesate transition state analog (TSA) to study a Zika virus NS3h helicase, which uses energy from ATP hydrolysis to reorganize ssRNA leading to completion of virus replication. The crystal structure of this TSA complex displays two conformations for a catalytically important loop, demonstrating how ATP hydrolysis can be coupled with RNA translocation. Unexpectedly, the trifluoromagnesate core of this transition state complex is octahedral. It is identified as having an unprecedented MgF<sub>3</sub>(Wat)<sup>–</sup> ligand, confirmed by <sup>19</sup>F NMR analysis. This structure was further probed by quantum mechanical calculations of the catalytic core (200 atoms), confirming the structural data interpretation and the concerted mechanism of ATP hydrolysis by this class of helicase. The formation of this MgF<sub>3</sub>(Wat)<sup>–</sup> ligand in helicase but not in other multiple MF<sub>x</sub> structures for ATPases and GTPases strongly implies they cannot possess such an additional water in their active sites.

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