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Antiamoebin I in Methanol Solution: Rapid Exchange between Right‐Handed and Left‐Handed 3 10 ‐Helical Conformations
Author(s) -
Shenkarev Zakhar O.,
Paramonov Alexander S.,
Nadezhdin Kirill D.,
Bocharov Eduard V.,
Kudelina Irina A.,
Skladnev Dmitry A.,
Tagaev Andrey A.,
Yakimenko Zoya A.,
Ovchinnikova Tatiana V.,
Arseniev Alexander S.
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790106
Subject(s) - chemistry , crystallography , right handed , stereochemistry , left handed , ionic bonding , population , amino acid , nuclear magnetic resonance spectroscopy , ion , organic chemistry , biochemistry , demography , sociology , physics , optics , nuclear physics , neutrino
Antiamoebin I (Aam‐I) is a membrane‐active peptaibol antibiotic isolated from fungal species belonging to the genera Cephalosporium, Emericellopsis, Gliocladium , and Stilbella. Antiamoebin I has the amino acid sequence: Ac‐Phe 1 ‐Aib‐Aib‐Aib‐Iva‐Gly‐Leu‐Aib 8 ‐Aib‐Hyp‐Gln‐Iva‐Hyp‐Aib‐Pro‐Phl 16 . By using the uniformly 13 C, 15 N‐labeled sample of Aam‐I, the set of conformationally dependent J couplings and 3h J NC couplings through H‐bonds were measured. Analysis of these data along with the data on magnetic nonequivalence of the 13 C β nuclei (Δ δ ( 13 C β )) in Aib and Iva residues allowed us to draw the univocal conclusion that the N‐terminal part (Phe 1 –Gly 6 ) of Aam‐I in MeOH solution is in fast exchange between the right‐handed and left‐handed 3 10 ‐helical conformations, with an approximately equal population of both states. An additional conformational exchange process was found at the Aib 8 residue. The 15 N‐NMR‐relaxation and CD‐spectroscopy measurements confirmed these findings. Molecular modeling and Monte Carlo simulations revealed that both exchange processes are correlated and coupled with significant hinge‐bending motions around the Aib 8 residue. Our results explain relatively low activity of Aam‐I with respect to other 15‐amino acid residue peptaibols (for example, zervamicin) in functional and biological tests. The high dynamic ‘propensity’ possibly prevents both initial binding of the antiamoebin to the membrane and subsequent formation of stable ionic channels according to the barrel‐stave mechanism.