Crystal structure of the channel-forming polypeptide antiamoebin in a membrane-mimetic environment

Karle, Isabella L.; Perozzo, Mary Ann; Mishra, Vinod; Balaram, Padmanabhan

doi:10.1073/pnas.95.10.5501

Cited by 68 publications

(47 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, disorder of the first five residues in one of the two molecules in the crystallographic asymmetric unit has been noted, with the data collected up to 1.4 . In another structure of antiamoebin I reported in the literature, at a resolution of 1.0 , Aib(2) has a torsion angle of f ¼ À56.58, y ¼ À43.48 [26]. Curiously, the first example of the crystal structure of an Aib-containing natural product was the cyclic tetrapeptide dihydrochlamydocin in which the Aib residue has f ¼ 71.98, y ¼ À63.78, corresponding to the C 7 /g-turn region of the Ramachandran map [46].…”

Section: Conformational Distributions In Peptide Crystalmentioning

confidence: 97%

Aib Residues in Peptaibiotics and Synthetic Sequences: Analysis of Nonhelical Conformations

Aravinda

Shamala

Balaram

2008

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

The alpha-aminoisobutyric (Aib) residue has generally been considered to be a strongly helicogenic residue as evidenced by its ability to promote helical folding in synthetic and natural sequences. Crystal structures of several peptide natural products, peptaibols, have revealed predominantly helical conformations, despite the presence of multiple helix-breaking Pro or Hyp residues. Survey of synthetic Aib-containing peptides shows a preponderance of 3(10)-, alpha-, and mixed 3(10)/alpha-helical structures. This review highlights the examples of Aib residues observed in nonhelical conformations, which fall 'primarily' into the polyproline II (P(II)) and fully extended regions of conformational space. The achiral Aib residue can adopt both left (alpha(L))- and right (alpha(R))-handed helical conformations. In sequences containing chiral amino acids, helix termination can occur by means of chiral reversal at an Aib residue, resulting in formation of a Schellman motif. Examples of Aib residues in unusual conformations are illustrated by surveying a database of Aib-containing crystal structures.

show abstract

Section: Conformational Distributions In Peptide Crystalmentioning

confidence: 97%

Aib Residues in Peptaibiotics and Synthetic Sequences: Analysis of Nonhelical Conformations

Aravinda

Shamala

Balaram

2008

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

show abstract

“…The long ( 16 amino acids) members of the family form ion channels in membranes, and in this way can act as antibiotics. In addition to NMR spectroscopic studies of a number of the peptiabols, (25±28) the crystal structures of three of the long peptaibols, alamethicin (ALA), (29) Leu1-zervamicin (ZER), (30) and antiamoebin (AAM) (31,32) have been determined (Fig. 3).…”

Section: Peptaibol Ion Channelsmentioning

confidence: 99%

Common structural features in gramicidin and other ion channels

Wallace

2000

Bioessays

View full text Add to dashboard Cite

“…Channel forming activity is mediated by formation of transbilayer helical bundles by these hydrophobic peptides (15,16,27). Efrapeptins are specific inhibitors of mitochondrial F 0 F 1 ATPase, but at higher concentrations the peptide behaves as a channel-forming ionophore (1).…”

Section: Discussionmentioning

confidence: 99%

Antimalarial Activities of Peptide Antibiotics Isolated from Fungi

Nagaraj

Uma

Shivayogi

et al. 2001

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Malaria caused by Plasmodium falciparum is a major public health problem in the developing countries of the world. Clinical treatment of malaria has become complicated due to the occurrence of infections caused by drug resistant parasites. Secondary metabolites from fungi are an attractive source of chemotherapeutic agents. This work reports the isolation and in vitro antiplasmodial activities of peptide antibiotics of fungal origin. The three peptide antibiotics used in this study were efrapeptins, zervamicins, and antiamoebin. The high-performance liquid chromatography-purified peptides were characterized by nuclear magnetic resonance and mass spectral analysis. All three fungal peptides kill P. falciparum in culture with 50% inhibitory concentrations in the micromolar range. A possible mode of action of these peptide antibiotics on P. falciparum is presented.Malaria is a major tropical disease that affects more than 300 million people living in the developing countries of the world (21, 24). The widespread occurrence of drug-resistant Plasmodium falciparum infection necessitates the urgent development of new chemotherapeutic agents. Secondary metabolites produced by fungi are often novel molecules with large potential for chemotherapeutic applications. Our aim has been to isolate, characterize, and screen fungal metabolites for their antimalarial properties. The secondary metabolites studied in this paper are efrapeptins, zervamicins, and antiamoebin. Table 1 lists the sequences of the peptides used in this study along with the fungal species that produce them. These compounds are peptide antibiotics, 16 amino acids long, that contain the unusual amino acids ␣-aminoisobutyric acid, isovaline, ␤-alanine, and hydroxyproline. Efrapeptins are produced by the fungus Tolypocladium niveum subsp. inflatum and are inhibitors of mitochondrial F 0 F 1 ATPase, some bacterial ATP synthases, and photophosphorylation in plants (1,13,14). The ATPase of the protozan parasite Trypanosoma cruzi is also inhibited by efrapeptins (7). Recently, efrapeptins have also been shown to inhibit exocytosis in an ATP-independent manner in eukaryotic cells (22). Both zervamicins and antiamoebin are uncouplers of mitochondrial oxidative phosphorylation (3,5,6,18). Antiamoebin exhibits trypanocidal activity in a mouse model for trypanosomiasis (19) and has been shown to possess anthelmintic properties (30). All three peptide antibiotics also act as channel-forming ionophores (18). Vial et al. have examined numerous other ionophores for antimalarial activity and found gramicidin D to be the most promising candidate under both in vivo and in vitro conditions (11,12). This work reports the purification, spectral characterization, and antimalarial activities of efrapeptins, zervamicins, and antiamoebin. ϩ human blood was prepared in the laboratory. The constituents of the fungal culture medium were obtained from HiMedia Laboratories, Mumbai, India. Silica gel (60 to 80 m) for medium-pressure liquid chromatography (MPLC) was supplied by Büchi Labo...

show abstract

Crystal structure of the channel-forming polypeptide antiamoebin in a membrane-mimetic environment

Cited by 68 publications

References 19 publications

Aib Residues in Peptaibiotics and Synthetic Sequences: Analysis of Nonhelical Conformations

Aib Residues in Peptaibiotics and Synthetic Sequences: Analysis of Nonhelical Conformations

Common structural features in gramicidin and other ion channels

Antimalarial Activities of Peptide Antibiotics Isolated from Fungi

Contact Info

Product

Resources

About