The Crystal Structure ofBurkholderia cenocepaciaDfsA Provides Insights into Substrate Recognition and Quorum Sensing Fatty Acid Biosynthesis

Biochemistry ◽  
2016 ◽  
Vol 55 (23) ◽  
pp. 3241-3250 ◽  
Author(s):  
Francesca Spadaro ◽  
Viola C. Scoffone ◽  
Laurent R. Chiarelli ◽  
Marco Fumagalli ◽  
Silvia Buroni ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Fatty Acid ◽  
Quorum Sensing ◽  
Fatty Acid Biosynthesis ◽  
Substrate Recognition ◽  
Acid Biosynthesis

scholarly journals The crystal structure of PfFabZ, the unique β-hydroxyacyl-ACP dehydratase involved in fatty acid biosynthesis of Plasmodium falciparum

2009 ◽  
Vol 14 (6) ◽  
pp. 1570-1580 ◽  
Author(s):  
Dirk Kostrewa ◽  
Fritz K. Winkler ◽  
Gerd Folkers ◽  
Leonardo Scapozza ◽  
Remo Perozzo
Keyword(s):  
Crystal Structure ◽  
Plasmodium Falciparum ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis

scholarly journals Mechanistic analysis of aliphatic β-lactones in Vibrio harveyi reveals a quorum sensing independent mode of action

2016 ◽  
Vol 52 (80) ◽  
pp. 11971-11974 ◽  
Author(s):  
Weining Zhao ◽  
Nicola Lorenz ◽  
Kirsten Jung ◽  
Stephan A. Sieber
Keyword(s):  
Fatty Acid ◽  
Quorum Sensing ◽  
Mode Of Action ◽  
Fatty Acid Biosynthesis ◽  
Vibrio Harveyi ◽  
Acid Biosynthesis ◽  
Mechanistic Analysis ◽  
Independent Mechanism ◽  
Independent Mode

β-Lactone analogs of autoinducers potently inhibitVibrio harveyibioluminescence using a quorum sensing independent mechanism interfering with fatty acid biosynthesis.

scholarly journals Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis

2005 ◽  
Vol 393 (2) ◽  
pp. 447-457 ◽  
Author(s):  
Sasala R. Wickramasinghe ◽  
Kirstine A. Inglis ◽  
Jonathan E. Urch ◽  
Sylke Müller ◽  
Daan M. F. van Aalten ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Plasmodium Falciparum ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Competitive Inhibition ◽  
Acyl Carrier Protein ◽  
Antimalarial Activity ◽  
Kinetic Properties ◽  
Carrier Protein ◽  
Acid Biosynthesis

Type II fatty acid biosynthesis represents an attractive target for the discovery of new antimalarial drugs. Previous studies have identified malarial ENR (enoyl acyl-carrier-protein reductase, or FabI) as the target for the antiseptic triclosan. In the present paper, we report the biochemical properties and 1.5 Å (1 Å=0.1 nm) crystal structure of OAR (3-oxoacyl acyl-carrier-protein reductase, or FabG), the second reductive step in fatty acid biosynthesis and its inhibition by hexachlorophene. Under optimal conditions of pH and ionic strength, Plasmodium falciparum OAR displays kinetic properties similar to those of OAR from bacteria or plants. Activity with NADH is <3% of that with NADPH. Fluorescence enhancement studies indicate that NADPH can bind to the free enzyme, consistent with kinetic and product inhibition studies suggesting a steady-state ordered mechanism. The crystal structure reveals a tetramer with a sulphate ion bound in the cofactor-binding site such that the side chains of the catalytic triad of serine, tyrosine and lysine are aligned in an active conformation, as previously observed in the Escherichia coli OAR–NADP+ complex. A cluster of positively charged residues is positioned at the entrance to the active site, consistent with the proposed recognition site for the physiological substrate (3-oxoacyl-acyl-carrier protein) in E. coli OAR. The antibacterial and anthelminthic agent hexachlorophene is a potent inhibitor of OAR (IC50 2.05 μM) displaying non-linear competitive inhibition with respect to NADPH. Hexachlorophene (EC50 6.2 μM) and analogues such as bithionol also have antimalarial activity in vitro, suggesting they might be useful leads for further development.

scholarly journals Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis

Cell Research ◽  
2016 ◽  
Vol 26 (12) ◽  
pp. 1330-1344 ◽  
Author(s):  
Lin Zhang ◽  
Jianfeng Xiao ◽  
Jianrong Xu ◽  
Tianran Fu ◽  
Zhiwei Cao ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Fatty Acid ◽  
Catalytic Mechanism ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis

Crystal Structure of MabA from Mycobacterium tuberculosis, a Reductase involved in Long-chain Fatty Acid Biosynthesis

2002 ◽  
Vol 320 (2) ◽  
pp. 249-261 ◽  
Author(s):  
Martin Cohen-Gonsaud ◽  
Stéphanie Ducasse ◽  
Francois Hoh ◽  
Didier Zerbib ◽  
Gilles Labesse ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Chain Fatty Acid ◽  
Acid Biosynthesis ◽  
Long Chain Fatty Acid ◽  
Long Chain

scholarly journals An aryl-homoserine lactone quorum-sensing signal produced by a dimorphic prosthecate bacterium

2018 ◽  
Vol 115 (29) ◽  
pp. 7587-7592 ◽  
Author(s):  
Lisheng Liao ◽  
Amy L. Schaefer ◽  
Bruna G. Coutinho ◽  
Pamela J. B. Brown ◽  
E. Peter Greenberg
Keyword(s):  
Fatty Acid ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Homoserine Lactone ◽  
Acid Biosynthesis ◽  
Acid Moiety ◽  
Coa Ligase ◽  
Prosthecate Bacterium

Many species ofProteobacteriaproduce acyl-homoserine lactone (AHL) compounds as quorum-sensing (QS) signals for cell density-dependent gene regulation. Most known AHL synthases, LuxI-type enzymes, produce fatty AHLs, and the fatty acid moiety is derived from an acyl-acyl carrier protein (ACP) intermediate in fatty acid biosynthesis. Recently, a class of LuxI homologs has been shown to use CoA-linked aromatic or amino acid substrates for AHL synthesis. By using an informatics approach, we found the CoA class of LuxI homologs exists primarily in α-Proteobacteria. The genome ofProsthecomicrobium hirschii, a dimorphic prosthecate bacterium, possesses aluxI-like AHL synthase gene that we predicted to encode a CoA-utilizing enzyme. We show theP. hirschiiLuxI homolog catalyzes synthesis of phenylacetyl-homoserine lactone (PA-HSL). Our experiments showP. hirschiiobtains phenylacetate from its environment and uses a CoA ligase to produce the phenylacetyl-CoA substrate for the LuxI homolog. By using an AHL degrading enzyme, we showed that PA-HSL controls aggregation, biofilm formation, and pigment production inP. hirschii. These findings advance a limited understanding of the CoA-dependent AHL synthases. We describe how to identify putative members of the class, we describe a signal synthesized by using an environmental aromatic acid, and we identify phenotypes controlled by the aryl-HSL.

Inhibition of early steps of de novo fatty-acid biosynthesis by different xenobiotica

1991 ◽  
Vol 81 (2) ◽  
pp. 251-255
Author(s):  
Manfred Focke ◽  
Andrea Feld ◽  
Hartmut K. Lichtenthaler
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Biosynthesis

Development of 'S', 'N’ Heterocycles as Antimycobacterials Targeting Fatty Acid Biosynthesis

2019 ◽  
Vol 15 ◽  
Author(s):  
L. K. Dahiwade ◽  
S. R. Rochlani ◽  
P. B. Choudhari ◽  
R. P. Dhavale ◽  
H. N. Moreira
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Antimycobacterial Activity ◽  
Drug Candidate ◽  
Causative Organism ◽  
Present Communication ◽  
Acid Biosynthesis ◽  
Rational Development ◽  
After Cancer ◽  
Drug Resistant Strains

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.

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