Modeling the secondary structures of the peptaibols antiamoebin I and zervamicin II modified with D-amino acids and proline analogues
authors Castro, TG; Micaelo, NM; Melle-Franco, M
nationality International
journal JOURNAL OF MOLECULAR MODELING
author keywords Noncanonical amino acids; Hydroxyproline analogues; Isovaline analogues; Molecular dynamics simulations; Peptaibols
keywords CHANNEL-FORMING POLYPEPTIDE; LINEAR CONSTRAINT SOLVER; ION CHANNELS; ANTIMICROBIAL PEPTIDES; MOLECULAR SIMULATION; CRYSTAL-STRUCTURE; ALPHA,ALPHA-DIALKYL GLYCINES; SPATIAL STRUCTURE; HELICAL PEPTIDES; WATER MODELS
abstract Antiamoebin I (AAM-I) and zervamicin II (Zrv-IIB) are peptaibols that exert antibiotic activity through the insertion/disruption of cell membranes. In this study, we investigated how the folding of these peptaibols are affected when some of their native residues are replaced with proline analogues and asymmetricalD-alpha, alpha-dialkyl glycines (two classes of noncanonical amino acids). Systematic substitutions of native Aib, Pro, Hyp, and Iva residues were performed to elucidate the folding properties of the modified peptaibols incorporating noncanonical residues. The secondary structure of a peptaibol influences its ability to incorporate into membranes and therefore its function. Our findings reveal that native Zrv-IIB unfolds considerably in water. The presence of Iva and the noncanonical proline analogue cis-3-amino-L-proline (ALP) in both peptaibols induces helical structures. Inserting asymmetric glycines such as alpha-methyl-D-leucine (MDL) and alpha-methyl-D-phenylalanine (MDP) into the peptaibols induces folding. This preorganization in water may help to overcome the energy barrier required for peptaibol insertion into the membrane, as well as to facilitate the formation of transmembrane channels.
publisher SPRINGER
issn 1610-2940
year published 2017
volume 23
issue 11
digital object identifier (doi) 10.1007/s00894-017-3479-5
web of science category Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications
subject category Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science
unique article identifier WOS:000413675400011
  ciceco authors
  impact metrics
journal analysis (jcr 2019):
journal impact factor 1.346
5 year journal impact factor 1.306
category normalized journal impact factor percentile 19.733
dimensions (citation analysis):
altmetrics (social interaction):



 


Sponsors

1suponsers_list_ciceco.jpg