The superfamily of mitochondrial Complex1_LYR motif-containing (LYRM) proteins

2013 ◽  
Vol 41 (5) ◽  
pp. 1335-1341 ◽  
Author(s):  
Heike Angerer
Keyword(s):  
Acyl Carrier Protein ◽  
Protein Complexes ◽  
Acid Synthesis ◽  
Acetate Metabolism ◽  
Carrier Protein ◽  
Type Ii ◽  
Protein Protein Interaction ◽  
Accessory Subunits ◽  
Ancient Proteins ◽  
The Common

Mitochondrial LYRM (leucine/tyrosine/arginine motif) proteins are members of the Complex1_LYR-like superfamily. Individual LYRM proteins have been identified as accessory subunits or assembly factors of mitochondrial OXPHOS (oxidative phosphorylation) complexes I, II, III and V respectively, and they play particular roles in the essential Fe–S cluster biogenesis and in acetate metabolism. LYRM proteins have been implicated in mitochondrial dysfunction, e.g. in the context of insulin resistance. However, the functional significance of the common LYRM is still unknown. Analysis of protein–protein interaction screens suggests that LYRM proteins form protein complexes with phylogenetically ancient proteins of bacterial origin. Interestingly, the mitochondrial FAS (fatty acid synthesis) type II acyl-carrier protein ACPM associates with some of the LYRM protein-containing complexes. Eukaryotic LYRM proteins interfere with mitochondrial homoeostasis and might function as adaptor-like ‘accessory factors’.

scholarly journals Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes

2016 ◽  
Vol 84 (12) ◽  
pp. 3597-3607 ◽  
Author(s):  
Jiangwei Yao ◽  
Megan E. Ericson ◽  
Matthew W. Frank ◽  
Charles O. Rock
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Carrier Protein ◽  
Type Ii ◽  
Intracellular Growth ◽  
Content Type ◽  
Bacterial Fatty Acid

Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogenListeria monocytogenesencode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype ofEscherichia colistrain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate ofL. monocytogenesin laboratory medium. Robust exogenous fatty acid incorporation was not detected inL. monocytogenesunless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth ofL. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth ofL. monocytogenes. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth ofL. monocytogenes.

scholarly journals Suppression offabBMutation byfabF1Is Mediated by Transcription Read-through in Shewanella oneidensis

2016 ◽  
Vol 198 (22) ◽  
pp. 3060-3069 ◽  
Author(s):  
Meng Li ◽  
Qiu Meng ◽  
Huihui Fu ◽  
Qixia Luo ◽  
Haichun Gao
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Tandem Repeats ◽  
Unsaturated Fatty Acids ◽  
Acyl Carrier Protein ◽  
Shewanella Oneidensis ◽  
Acid Synthesis ◽  
Carrier Protein ◽  
Type Ii ◽  
Content Type

ABSTRACTAs type II fatty acid synthesis is essential for the growth ofEscherichia coli, its many components are regarded as potential targets for novel antibacterial drugs. Among them, β-ketoacyl-acyl carrier protein (ACP) synthase (KAS) FabB is the exclusive factor for elongation of thecis-3-decenoyl-ACP (cis-3-C10-ACP). In our previous study, we presented evidence to suggest that this may not be the case inShewanella oneidensis, an emerging model gammaproteobacterium renowned for its respiratory versatility. Here, we identified FabF1, another KAS, as a functional replacement for FabB inS. oneidensis. InfabB+ordesA+(encoding a desaturase) cells, which are capable of making unsaturated fatty acids (UFA), FabF1 is barely produced. However, UFA auxotroph mutants devoid of bothfabBanddesAgenes can be spontaneously converted to suppressor strains, which no longer require exogenous UFAs for growth. Suppression is caused by a TGTTTT deletion in the region upstream of thefabF1gene, resulting in enhanced FabF1 production. We further demonstrated that the deletion leads to transcription read-through of the terminator foracpP, an acyl carrier protein gene immediately upstream offabF1. There are multiple tandem repeats in the region covering the terminator, and the TGTTTT deletion, as well as others, compromises the terminator efficacy. In addition, FabF2 also shows an ability to complement the FabB loss, albeit substantially less effectively than FabF1.IMPORTANCEIt has been firmly established that FabB for UFA synthesis via type II fatty acid synthesis in FabA-containing bacteria such asE. coliis essential. However,S. oneidensisappears to be an exception. In this bacterium, FabF1, when sufficiently expressed, is able to fully complement the FabB loss. Importantly, such a capability can be obtained by spontaneous mutations, which lead to transcription read-through. Therefore, our data, by identifying the functional overlap between FabB and FabFs, provide new insights into the current understanding of KAS and help reveal novel ways to block UFA synthesis for therapeutic purposes.

scholarly journals Structure of the mitochondrial β-ketoacyl-[acyl carrier protein] synthase fromArabidopsisand its role in fatty acid synthesis

FEBS Letters ◽  
2004 ◽  
Vol 577 (1-2) ◽  
pp. 170-174 ◽  
Author(s):  
Johan G. Olsen ◽  
Anne V. Rasmussen ◽  
Penny von Wettstein-Knowles ◽  
Anette Henriksen
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Carrier Protein

scholarly journals The 1.3-Angstrom-Resolution Crystal Structure of β-Ketoacyl-Acyl Carrier Protein Synthase II from Streptococcus pneumoniae

2003 ◽  
Vol 185 (14) ◽  
pp. 4136-4143 ◽  
Author(s):  
Allen C. Price ◽  
Charles O. Rock ◽  
Stephen W. White
Keyword(s):  
Crystal Structure ◽  
Streptococcus Pneumoniae ◽  
Active Site ◽  
Acyl Carrier Protein ◽  
Substrate Binding ◽  
Acid Synthesis ◽  
Imidazole Ring ◽  
Antibacterial Drug ◽  
Carrier Protein ◽  
Essential Components

ABSTRACT The β-ketoacyl-acyl carrier protein synthases are members of the thiolase superfamily and are key regulators of bacterial fatty acid synthesis. As essential components of the bacterial lipid metabolic pathway, they are an attractive target for antibacterial drug discovery. We have determined the 1.3 Å resolution crystal structure of the β-ketoacyl-acyl carrier protein synthase II (FabF) from the pathogenic organism Streptococcus pneumoniae. The protein adopts a duplicated βαβαβαββ fold, which is characteristic of the thiolase superfamily. The two-fold pseudosymmetry is broken by the presence of distinct insertions in the two halves of the protein. These insertions have evolved to bind the specific substrates of this particular member of the thiolase superfamily. Docking of the pantetheine moiety of the substrate identifies the loop regions involved in substrate binding and indicates roles for specific, conserved residues in the substrate binding tunnel. The active site triad of this superfamily is present in spFabF as His 303, His 337, and Cys 164. Near the active site is an ion pair, Glu 346 and Lys 332, that is conserved in the condensing enzymes but is unusual in our structure in being stabilized by an Mg2+ ion which interacts with Glu 346. The active site histidines interact asymmetrically with Lys 332, whose positive charge is closer to His 303, and we propose a specific role for the lysine in polarizing the imidazole ring of this histidine. This asymmetry suggests that the two histidines have unequal roles in catalysis and provides new insights into the catalytic mechanisms of these enzymes.

scholarly journals A Light‐Activated Acyl Carrier Protein “Trap” for Intermediate Capture in Type II Iterative Polyketide Biocatalysis

2019 ◽  
Vol 25 (72) ◽  
pp. 16515-16518
Author(s):  
Samantha L. Kilgour ◽  
David P. A. Kilgour ◽  
Panward Prasongpholchai ◽  
Peter B. O'Connor ◽  
Manuela Tosin
Keyword(s):  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Type Ii

Acyl carrier protein is a bacterial cytoplasmic target of cationic antimicrobial peptide LL-37

2015 ◽  
Vol 470 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Myung-Chul Chung ◽  
Scott N. Dean ◽  
Monique L. van Hoek
Keyword(s):  
Antimicrobial Peptide ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Membrane Disruption ◽  
Carrier Protein ◽  
Cytoplasmic Protein ◽  
Bacterial Killing ◽  
Cationic Antimicrobial Peptide ◽  
Antibiotic Resistant ◽  
Future Drug

In addition to membrane disruption, the cathelicidin antimicrobial peptide LL-37 translocates through the bacterial inner membrane to target intracellular molecules. Our data suggest that the CAMP LL-37 is able can specifically bind to the cytoplasmic protein AcpP resulting in the inhibition of fatty acid synthesis and bacterial killing. Our studies introduce a novel mechanism for cationic antimicrobial peptides, which may be useful in future drug development for the treatment of antibiotic-resistant bacterial infection.

Sign in / Sign up

Export Citation Format

Share Document