Cationic and Anionic Dinuclear Nickel Complexes [Ni(N2S2)Ni(dtc)]n(n=−1, +1) Modeling the Active Site of Acetyl-CoA Synthase

2009 ◽  
Vol 38 (2) ◽  
pp. 184-185 ◽  
Author(s):  
Yumei Song ◽  
Mikinao Ito ◽  
Mai Kotera ◽  
Tsuyoshi Matsumoto ◽  
Kazuyuki Tatsumi
Keyword(s):  
Active Site ◽  
Nickel Complexes ◽  
Acetyl Coa

Structural Models for the Active Site of Acetyl-CoA Synthase: Synthesis of Dinuclear Nickel Complexes Having Thiolate, Isocyanide, and Thiourea on the NipSite

2009 ◽  
Vol 48 (3) ◽  
pp. 1250-1256 ◽  
Author(s):  
Mikinao Ito ◽  
Mai Kotera ◽  
Yumei Song ◽  
Tsuyoshi Matsumoto ◽  
Kazuyuki Tatsumi
Keyword(s):  
Active Site ◽  
Nickel Complexes ◽  
Structural Models ◽  
Acetyl Coa

Sirtuin-dependent reversible lysine acetylation controls the activity of acetyl-Coenzyme A synthetase in Campylobacter jejuni

2021 ◽  
Author(s):  
Victoria L. Jeter ◽  
Jorge C. Escalante-Semerena
Keyword(s):  
Campylobacter Jejuni ◽  
Posttranslational Modifications ◽  
Active Site ◽  
Protein Function ◽  
Metabolic Enzyme ◽  
Lysine Acetylation ◽  
Class Iii ◽  
Acetyl Coa

Posttranslational modifications are mechanisms for rapid control of protein function used by cells from all domains of life. Acetylation of the epsilon amino group ( N ε ) of an active-site lysine of the AMP-forming acetyl-CoA synthetase (Acs) enzyme is the paradigm for the posttranslational control of the activity of metabolic enzymes. In bacteria, the alluded active-site lysine of Acs enzymes can be modified by a number of different GCN5-type N -acetyltransferases (GNATs). Acs activity is lost as a result of acetylation, and restored by deacetylation. Using a heterologous host, we show that Campylobacter jejuni NCTC11168 synthesizes enzymes that control Acs function by reversible lysine acetylation (RLA). This work validates the function of gene products encoded by the cj1537c , cj1715, and cj1050c loci, namely the AMP-forming acetate:CoA ligase ( Cj Acs), a type IV GCN5-type lysine acetyltransferase (GNAT, hereafter Cj LatA), and a NAD + -dependent (class III) sirtuin deacylase ( Cj CobB), respectively. To our knowledge, these are the first in vivo and in vitro data on C. jejuni enzymes that control the activity of Cj Acs. IMPORTANCE This work is important because it provides the experimental evidence needed to support the assignment of function to three key enzymes, two of which control the reversible posttranslational modification of an active-site lysyl residue of the central metabolic enzyme acetyl-CoA synthetase ( Cj Acs). We can now generate Campylobacter jejuni mutant strains defective in these functions, so we can establish the conditions in which this mode of regulation of Cj Acs is triggered in this bacterium. Such knowledge may provide new therapeutic strategies for the control of this pathogen.

Hydrolytically Active Tetranuclear Nickel Complexes with Structural Resemblance to the Active Site of Urease

2002 ◽  
Vol 41 (20) ◽  
pp. 4981-4983 ◽  
Author(s):  
Håkan Carlsson ◽  
Matti Haukka ◽  
Ebbe Nordlander
Keyword(s):  
Active Site ◽  
Nickel Complexes ◽  
Structural Resemblance

scholarly journals Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu

2020 ◽  
Vol 48 (10) ◽  
pp. 5294-5305
Author(s):  
Shweta Karambelkar ◽  
Shubha Udupa ◽  
Vykuntham Naga Gowthami ◽  
Sharmila Giliyaru Ramachandra ◽  
Ganduri Swapna ◽  
...  
Keyword(s):  
Active Site ◽  
Metal Binding ◽  
Broad Host Range ◽  
Dna Modification ◽  
Bacteriophage Mu ◽  
Acetyl Coa ◽  
Protein Architecture ◽  
Iron Binding Protein ◽  
Free Radical Chemistry ◽  
Computational Analyses

Abstract The broad host range bacteriophage Mu employs a novel ‘methylcarbamoyl’ modification to protect its DNA from diverse restriction systems of its hosts. The DNA modification is catalyzed by a phage-encoded protein Mom, whose mechanism of action is a mystery. Here, we characterized the co-factor and metal-binding properties of Mom and provide a molecular mechanism to explain ‘methylcarbamoyl’ation of DNA by Mom. Computational analyses revealed a conserved GNAT (GCN5-related N-acetyltransferase) fold in Mom. We demonstrate that Mom binds to acetyl CoA and identify the active site. We discovered that Mom is an iron-binding protein, with loss of Fe2+/3+-binding associated with loss of DNA modification activity. The importance of Fe2+/3+ is highlighted by the colocalization of Fe2+/3+ with acetyl CoA within the Mom active site. Puzzlingly, acid-base mechanisms employed by >309,000 GNAT members identified so far, fail to support methylcarbamoylation of adenine using acetyl CoA. In contrast, free-radical chemistry catalyzed by transition metals like Fe2+/3+ can explain the seemingly challenging reaction, accomplished by collaboration between acetyl CoA and Fe2+/3+. Thus, binding to Fe2+/3+, a small but unprecedented step in the evolution of Mom, allows a giant chemical leap from ordinary acetylation to a novel methylcarbamoylation function, while conserving the overall protein architecture.

scholarly journals Functional copper at the acetyl-CoA synthase active site

2003 ◽  
Vol 100 (7) ◽  
pp. 3689-3694 ◽  
Author(s):  
J. Seravalli ◽  
W. Gu ◽  
A. Tam ◽  
E. Strauss ◽  
T. P. Begley ◽  
...  
Keyword(s):  
Active Site ◽  
Acetyl Coa

scholarly journals Pyruvate carboxylase catalysis of phosphate transfer between carbamoyl phosphate and ADP

1991 ◽  
Vol 273 (2) ◽  
pp. 443-448 ◽  
Author(s):  
P V Attwood ◽  
B D L A Graneri
Keyword(s):  
Active Site ◽  
Pyruvate Carboxylase ◽  
Reverse Reaction ◽  
Carbamoyl Phosphate ◽  
Acetyl Coa ◽  
Essential Requirement ◽  
Pyruvate Carboxylation ◽  
Ionizable Residues ◽  
Ph Profiles

In a reaction that is analogous to the phosphorylation of ADP from carboxyphosphate, pyruvate carboxylase catalyses the formation of ATP from carbamoyl phosphate and ADP at a rate that is about 0.3% of the pyruvate-carboxylation reaction and about 3% of the full reverse reaction. Acetyl-CoA stimulates the phosphorylation of ADP from carbamoyl phosphate but is not an essential requirement of the reaction. Mg2+ also stimulates the reaction, and in the range of Mg2+ concentrations considered the effect of V is much larger in the absence of acetyl-CoA than in its presence. Acetyl-CoA and Mg2+ may be acting in a co-operative way to stimulate the phosphorylation of ADP in a similar way to their effects on the pyruvate-carboxylation reaction. The phosphorylation of ADP by carbamoyl phosphate is also stimulated by the presence of biotin in the part of the active site where this reaction occurs, but again it is not absolutely required for the reaction to proceed. The pH profiles of the phosphorylation of ADP by carbamoyl phosphate indicate that there are at least two ionizable residues involved in the reaction, one of which probably has a role in the release of carbamate from the active site.

scholarly journals Bicarbonate-dependent ATP cleavage catalysed by pyruvate carboxylase in the absence of pyruvate

1992 ◽  
Vol 287 (3) ◽  
pp. 1011-1017 ◽  
Author(s):  
P V Attwood ◽  
B D L A Graneri
Keyword(s):  
Reaction Mechanism ◽  
Atpase Activity ◽  
Active Site ◽  
Pyruvate Carboxylase ◽  
Substrate Inhibition ◽  
Cleavage Reaction ◽  
Acetyl Coa ◽  
Enzyme Preparations ◽  
Pyruvate Carboxylation ◽  
Rate Of Movement

Preparations of pyruvate carboxylase catalyse the cleavage of MgATP in the absence of pyruvate and acetyl-CoA. The rate of this cleavage is higher in the presence of HCO3- than in its absence. Incubation of the enzyme preparations with an excess of the pyruvate carboxylase inhibitor, avidin, completely abolishes the pyruvate carboxylating activity of the enzyme preparations but only abolishes the HCO3(-)-dependent MgATP cleaving activity, with no effect on the HCO3(-)-independent ATPase activity. The HCO3(-)-dependent MgATP cleavage is also sensitive to inhibition by a pyruvate carboxylase inhibitor, oxamate, and the dependence of the reaction on the free Mg2+ concentration is similar to that of the pyruvate-carboxylation reaction, whereas the HCO3(-)-independent MgATP cleavage is not dependent on the concentration of free Mg2+ in the range tested. This indicates that MgATP cleavage by pyruvate carboxylase is entirely dependent on the presence of HCO3- and that there may be a low level of ATPase contamination in the enzyme preparations. In addition, inhibition of the HCO3(-)-dependent MgATP cleavage by both avidin and oxamate indicate that although biotin does not directly participate in the reaction, its presence is required in that part of the active site of the enzyme. The rate of HCO3(-)-dependent MgATP cleavage is about 0.07% of that of the full pyruvate carboxylation reaction under similar conditions with saturating substrates. The reaction mechanism is sequential with respect to MgATP and HCO3- addition and Mg2+ adds at equilibrium before MgATP. Acetyl-CoA stimulates the HCO3(-)-dependent MgATP cleavage at low MgATP concentrations, with the stimulation being greater at low Mg2+ concentrations. At high levels of MgATP in the presence of acetyl-CoA, substrate inhibition is evident and is more pronounced at increasing concentrations of Mg2+. This inhibition appears to be, at least in part, caused by inhibition of decarboxylation of the enzyme-carboxybiotin complex by the binding to this complex of Mg2+ and MgATP, which probably act to reduce the rate of movement of carboxybiotin from the site of the MgATP cleavage reaction to that of the pyruvate carboxylation reaction where it is unstable and decarboxylates.

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