A Shared Binding Site for NAD+and Coenzyme A in an Acetaldehyde Dehydrogenase Involved in Bacterial Degradation of Aromatic Compounds†

Biochemistry ◽  
2008 ◽  
Vol 47 (26) ◽  
pp. 6870-6882 ◽  
Author(s):  
Yu Lei ◽  
Peter D. Pawelek ◽  
Justin Powlowski
Keyword(s):  
Binding Site ◽  
Aromatic Compounds ◽  
Coenzyme A ◽  
Bacterial Degradation ◽  
Acetaldehyde Dehydrogenase

scholarly journals Epoxy Coenzyme A Thioester Pathways for Degradation of Aromatic Compounds

2012 ◽  
Vol 78 (15) ◽  
pp. 5043-5051 ◽  
Author(s):  
Wael Ismail ◽  
Johannes Gescher
Keyword(s):  
Aromatic Ring ◽  
Aromatic Compounds ◽  
Coenzyme A ◽  
Environmental Pollutants ◽  
Bacterial Degradation ◽  
Ring Cleavage ◽  
The Novel ◽  
Energy Consuming ◽  
Coa Thioesters ◽  
Hydrolytic Mechanism

ABSTRACTAromatic compounds (biogenic and anthropogenic) are abundant in the biosphere. Some of them are well-known environmental pollutants. Although the aromatic nucleus is relatively recalcitrant, microorganisms have developed various catabolic routes that enable complete biodegradation of aromatic compounds. The adopted degradation pathways depend on the availability of oxygen. Under oxic conditions, microorganisms utilize oxygen as a cosubstrate to activate and cleave the aromatic ring. In contrast, under anoxic conditions, the aromatic compounds are transformed to coenzyme A (CoA) thioesters followed by energy-consuming reduction of the ring. Eventually, the dearomatized ring is opened via a hydrolytic mechanism. Recently, novel catabolic pathways for the aerobic degradation of aromatic compounds were elucidated that differ significantly from the established catabolic routes. The new pathways were investigated in detail for the aerobic bacterial degradation of benzoate and phenylacetate. In both cases, the pathway is initiated by transforming the substrate to a CoA thioester and all the intermediates are bound by CoA. The subsequent reactions involve epoxidation of the aromatic ring followed by hydrolytic ring cleavage. Here we discuss the novel pathways, with a particular focus on their unique features and occurrence as well as ecological significance.

Binding site for fungal β-lactone hymeglusin on cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase

2004 ◽  
Vol 1636 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Hiroshi Tomoda ◽  
Naomi Ohbayashi ◽  
Yuko Morikawa ◽  
Hidetoshi Kumagai ◽  
Satoshi Ōmura
Keyword(s):  
Binding Site ◽  
Coenzyme A

scholarly journals The nature of the binding site for aromatic compounds in glycogen phosphorylase b

1975 ◽  
Vol 147 (2) ◽  
pp. 369-371 ◽  
Author(s):  
G Soman ◽  
G Philip
Keyword(s):  
Chemical Modification ◽  
Binding Site ◽  
Aromatic Compounds ◽  
Glycogen Phosphorylase ◽  
Relative Effectiveness ◽  
Rabbit Muscle ◽  
Substituent Constant ◽  
Chemically Modified ◽  
Glycogen Phosphorylase B ◽  
Hydrophobic Nature

The inhibition of rabbit muscle glycogen phosphorylase b (1,4-alpha-D-glucan--orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) by aromatic compounds was examined with 15 compounds. The relative effectiveness of the inhibitors correlated well with increasing substituent constant, pi, indicating the hydrophobic nature of the binding site. The inhibition was not affected by the ionic-strength variation of the assay mixtures. The results predict that the course of chemical modification of this enzyme and the properties of the derivatives depend on the nature of the reagent and on the incorporated groups. Many of the dissimilar and sometimes contradictory results reported for chemical-modification studies and for chemically modified phosphorylase b are explained by the findings presented in the paper.

scholarly journals Bacterial Conversion of Hydroxylamino Aromatic Compounds by both Lyase and Mutase Enzymes Involves Intramolecular Transfer of Hydroxyl Groups

2003 ◽  
Vol 69 (5) ◽  
pp. 2786-2793 ◽  
Author(s):  
Lloyd J. Nadeau ◽  
Zhongqi He ◽  
Jim C. Spain
Keyword(s):  
Aromatic Compounds ◽  
Ralstonia Eutropha ◽  
Transfer Mechanism ◽  
Bacterial Degradation ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Reaction Products ◽  
Comamonas Acidovorans ◽  
Label Incorporation ◽  
Intramolecular Transfer

ABSTRACT Hydroxylamino aromatic compounds are converted to either the corresponding aminophenols or protocatechuate during the bacterial degradation of nitroaromatic compounds. The origin of the hydroxyl group of the products could be the substrate itself (intramolecular transfer mechanism) or the solvent water (intermolecular transfer mechanism). The conversion of hydroxylaminobenzene to 2-aminophenol catalyzed by a mutase from Pseudomonas pseudoalcaligenes JS45 proceeds by an intramolecular hydroxyl transfer. The conversions of hydroxylaminobenzene to 2- and 4-aminophenol by a mutase from Ralstonia eutropha JMP134 and to 4-hydroxylaminobenzoate to protocatechuate by a lyase from Comamonas acidovorans NBA-10 and Pseudomonas sp. strain 4NT were proposed, but not experimentally proved, to proceed by the intermolecular transfer mechanism. GC-MS analysis of the reaction products formed in H2 18O did not indicate any 18O-label incorporation during the conversion of hydroxylaminobenzene to 2- and 4-aminophenols catalyzed by the mutase from R. eutropha JMP134. During the conversion of 4-hydroxylaminobenzoate catalyzed by the hydroxylaminolyase from Pseudomonas sp. strain 4NT, only one of the two hydroxyl groups in the product, protocatechuate, was 18O labeled. The other hydroxyl group in the product must have come from the substrate. The mutase in strain JS45 converted 4-hydroxylaminobenzoate to 4-amino-3-hydroxybenzoate, and the lyase in Pseudomonas strain 4NT converted hydroxylaminobenzene to aniline and 2-aminophenol but not to catechol. The results indicate that all three types of enzyme-catalyzed rearrangements of hydroxylamino aromatic compounds proceed via intramolecular transfer of hydroxyl groups.

Coenzyme-A-binding site of chloramphenicol acetyltransferase

1988 ◽  
Vol 16 (5) ◽  
pp. 715-716 ◽  
Author(s):  
PHILIP J. DAY ◽  
ANN LEWENDON ◽  
WILLIAM V. SHAW
Keyword(s):  
Binding Site ◽  
Coenzyme A ◽  
Chloramphenicol Acetyltransferase

scholarly journals Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica

2018 ◽  
Vol 115 (15) ◽  
pp. 3846-3851 ◽  
Author(s):  
Percival Yang-Ting Chen ◽  
Heather Aman ◽  
Mehmet Can ◽  
Stephen W. Ragsdale ◽  
Catherine L. Drennan
Keyword(s):  
Carbon Dioxide ◽  
Binding Site ◽  
Coenzyme A ◽  
Structural Data ◽  
Thiamine Pyrophosphate ◽  
Sequence Motifs ◽  
Moorella Thermoacetica ◽  
Microbial Enzyme ◽  
Pyruvate:Ferredoxin Oxidoreductase ◽  
Domain Iii

Pyruvate:ferredoxin oxidoreductase (PFOR) is a microbial enzyme that uses thiamine pyrophosphate (TPP), three [4Fe-4S] clusters, and coenzyme A (CoA) in the reversible oxidation of pyruvate to generate acetyl-CoA and carbon dioxide. The two electrons that are generated as a result of pyruvate decarboxylation are used in the reduction of low potential ferredoxins, which provide reducing equivalents for central metabolism, including the Wood–Ljungdahl pathway. PFOR is a member of the 2-oxoacid:ferredoxin oxidoreductase (OFOR) superfamily, which plays major roles in both microbial redox reactions and carbon dioxide fixation. Here, we present a set of crystallographic snapshots of the best-studied member of this superfamily, the PFOR from Moorella thermoacetica (MtPFOR). These snapshots include the native structure, those of lactyl-TPP and acetyl-TPP reaction intermediates, and the first of an OFOR with CoA bound. These structural data reveal the binding site of CoA as domain III, the function of which in OFORs was previously unknown, and establish sequence motifs for CoA binding in the OFOR superfamily. MtPFOR structures further show that domain III undergoes a conformational change upon CoA binding that seals off the active site and positions the thiolate of CoA directly adjacent to the TPP cofactor. These structural findings provide a molecular basis for the experimental observation that CoA binding accelerates catalysis by 105-fold.

Anaerobic degradation of homocyclic aromatic compounds via arylcarboxyl-coenzyme A esters: organisms, strategies and key enzymes

2013 ◽  
Vol 16 (3) ◽  
pp. 612-627 ◽  
Author(s):  
Matthias Boll ◽  
Claudia Löffler ◽  
Brandon E. L. Morris ◽  
Johannes W. Kung
Keyword(s):  
Aromatic Compounds ◽  
Anaerobic Degradation ◽  
Coenzyme A ◽  
Key Enzymes ◽  
Coenzyme A Esters

scholarly journals Point Mutations In Candida Glabrata 3-Hydroxy-3-Methyl Glutaryl Coenzyme A Reductase (HMGRCg) An Antifungal Target, Decrease Enzymatic Activity And Substrate/Inhibitor Affinity

2021 ◽  
Author(s):  
Dulce Andrade-Pavón ◽  
Vanessa Fernández-Muñoz ◽  
Wendy González-Ibarra ◽  
César Hernández-Rodríguez ◽  
J. Antonio Ibarra ◽  
...  
Keyword(s):  
Binding Energy ◽  
Enzymatic Activity ◽  
Binding Site ◽  
Candida Glabrata ◽  
Coenzyme A ◽  
Substrate Binding ◽  
Point Mutations ◽  
Substrate Binding Site ◽  
Substrate Inhibitor ◽  
Coenzyme A Reductase

Abstract An alternative target for antifungal drugs is 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR), a key enzyme in the ergosterol biosynthesis pathway. The aim of this study was to obtain, purify, characterize, and overexpress five point mutations in highly conserved regions of the catalytic domain of Candida glabrata HMGR (HMGRCg) to explore the function of key amino acid residues. Glutamic acid (Glu) was substituted by glutamine in the E680Q mutant (at the dimerization site), Glu by glutamine in E711Q (at the substrate binding site), aspartic acid by alanine in D805A and methionine by arginine in M807R (the latter two at the cofactor binding site). A double mutation, E680Q-M807R, was also made. The in vitro enzymatic activity decreased significantly in all recombinant (versus wild-type) HMGRCg, and the in silico binding energy for simvastatin, alpha-asarone and the substrate HMG-CoA was also lower for the mutants. The lowest enzymatic activity and binding energy was displayed by E711Q, suggesting that Glu711 (in the substrate binding site) is an important residue for enzymatic activity. The double mutant HMGRCg E680Q-M807R exhibited the second lowest enzymatic activity. The current findings provide insights into the role of residues in the catalytic site of HMGRCg.

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