scholarly journals Insight into the Key Structural Features of Potent Enoyl Acyl Carrier Protein Reductase Inhibitors Based on Computer Aided Molecular Design

10.5772/27931 ◽  
2011 ◽  
Author(s):  
Auradee Punkvang ◽  
Pharit Kamsri ◽  
Kodchakon Kun-asa ◽  
Patchreenart Saparpakorn ◽  
Supa Hannongbua ◽  
...  
Keyword(s):  
Molecular Design ◽  
Acyl Carrier Protein ◽  
Structural Features ◽  
Carrier Protein ◽  
Reductase Inhibitors ◽  
Computer Aided ◽  
Insight Into

scholarly journals Computer-aided discovery of antimicrobial agents as potential enoyl acyl carrier protein reductase inhibitors

2017 ◽  
Vol 16 (2) ◽  
pp. 397 ◽  
Author(s):  
Mohammad A Ghattas ◽  
Nermin A Eissa ◽  
Sanaa K Bardaweel ◽  
Abdallah Abu Mellal ◽  
Noor Atatreh
Keyword(s):  
Antimicrobial Agents ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Reductase Inhibitors ◽  
Computer Aided

Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein‐Linked Extender Units in Ansamitocin Biosynthesis

ChemBioChem ◽  
2020 ◽  
Vol 21 (9) ◽  
pp. 1309-1314 ◽  
Author(s):  
Fa Zhang ◽  
Huining Ji ◽  
Imtiaz Ali ◽  
Zixin Deng ◽  
Linquan Bai ◽  
...  
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Insight Into

scholarly journals 3D-QSAR studies of quinoline Schiff bases as enoyl acyl carrier protein reductase inhibitors

2014 ◽  
pp. 59
Author(s):  
Shrinivas Joshi ◽  
Sheshagiri Dixit ◽  
Uttam More ◽  
Devendra Kumar ◽  
Tejraj Aminabhavi ◽  
...  
Keyword(s):  
Schiff Bases ◽  
Acyl Carrier Protein ◽  
3D Qsar ◽  
Carrier Protein ◽  
Qsar Studies ◽  
Reductase Inhibitors

Acyl carrier protein: structure–function relationships in a conserved multifunctional protein family

2007 ◽  
Vol 85 (6) ◽  
pp. 649-662 ◽  
Author(s):  
David M. Byers ◽  
Huansheng Gong
Keyword(s):  
Fatty Acid ◽  
Active Sites ◽  
Fatty Acid Synthase ◽  
Acyl Carrier Protein ◽  
Divalent Cations ◽  
Structural Features ◽  
Carrier Protein ◽  
Type I ◽  
Prosthetic Group

Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a separate domain within a large multifunctional fatty acid synthase polyprotein (type I FAS), whereas it is a small monomeric protein in bacteria and plastids (type II FAS). Bacterial ACPs are also acyl donors for synthesis of a variety of products, including endotoxin and acylated homoserine lactones involved in quorum sensing; the distinct and essential nature of these processes in growth and pathogenesis make ACP-dependent enzymes attractive antimicrobial drug targets. Additionally, ACP homologues are key components in the production of secondary metabolites such as polyketides and nonribosomal peptides. Many ACPs exhibit characteristic structural features of natively unfolded proteins in vitro, with a dynamic and flexible conformation dominated by 3 parallel α helices that enclose the thioester-linked acyl group attached to a phosphopantetheine prosthetic group. ACP conformation may also be influenced by divalent cations and interaction with partner enzymes through its “recognition” helix II, properties that are key to its ability to alternately sequester acyl groups and deliver them to the active sites of ACP-dependent enzymes. This review highlights recent progress in defining how the structural features of ACP are related to its multiple carrier roles in fatty acid metabolism.

scholarly journals The genome of a Bacteroidetes inhabitant of the human gut encodes a structurally distinct enoyl-acyl carrier protein reductase (FabI)

2020 ◽  
Vol 295 (22) ◽  
pp. 7635-7652
Author(s):  
Christopher D. Radka ◽  
Matthew W. Frank ◽  
Jiangwei Yao ◽  
Jayaraman Seetharaman ◽  
Darcie J. Miller ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Change ◽  
Conformational Changes ◽  
Active Site ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Binding Pocket ◽  
Structural Features ◽  
Antibacterial Drug ◽  
Carrier Protein

Enoyl-acyl carrier protein reductase (FabI) catalyzes a rate-controlling step in bacterial fatty-acid synthesis and is a target for antibacterial drug development. A phylogenetic analysis shows that FabIs fall into four divergent clades. Members of clades 1–3 have been structurally and biochemically characterized, but the fourth clade, found in members of phylum Bacteroidetes, is uncharacterized. Here, we identified the unique structure and conformational changes that distinguish clade 4 FabIs. Alistipes finegoldii is a prototypical Bacteroidetes inhabitant of the gut microbiome. We found that A. finegoldii FabI (AfFabI) displays cooperative kinetics and uses NADH as a cofactor, and its crystal structure at 1.72 Å resolution showed that it adopts a Rossmann fold as do other characterized FabIs. It also disclosed a carboxyl-terminal extension that forms a helix–helix interaction that links the protomers as a unique feature of AfFabI. An AfFabI·NADH crystal structure at 1.86 Å resolution revealed that this feature undergoes a large conformational change to participate in covering the NADH-binding pocket and establishing the water channels that connect the active site to the central water well. Progressive deletion of these interactions led to catalytically compromised proteins that fail to bind NADH. This unique conformational change imparted a distinct shape to the AfFabI active site that renders it refractory to a FabI drug that targets clade 1 and 3 pathogens. We conclude that the clade 4 FabI, found in the Bacteroidetes inhabitants of the gut, have several structural features and conformational transitions that distinguish them from other bacterial FabIs.

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