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Structural Characterization of Histatin 5-Spermidine Conjugates : A Combined Experimental and Theoretical Study

Jephthah, Stephanie LU ; Henriques, Joao LU ; Cragnell, Carolina LU ; Puri, Sumant; Edgerton, Mira and Skepö, Marie LU (2017) In Journal of Chemical Information and Modeling2005-01-01+01:00 57(6). p.1330-1341
Abstract

Histatin 5 (Hst5) is a naturally occurring antimicrobial peptide that acts as the first line of defense against oral candidiasis. It has been shown that conjugation of the active Hst5 fragment, Hst54-15, and the polyamine spermidine (Spd) improves the candidacidal effect. Knowledge about the structure of these conjugates is, however, very limited. Thus, the aim of this study was to characterize the structural properties of the Hst54-15-Spd conjugates by performing atomistic molecular dynamics simulations in combination with small-angle X-ray scattering. It was shown that the Hst54-15-Spd conjugates adopt extended and slightly rigid random coil conformations without any secondary structure in aqueous... (More)

Histatin 5 (Hst5) is a naturally occurring antimicrobial peptide that acts as the first line of defense against oral candidiasis. It has been shown that conjugation of the active Hst5 fragment, Hst54-15, and the polyamine spermidine (Spd) improves the candidacidal effect. Knowledge about the structure of these conjugates is, however, very limited. Thus, the aim of this study was to characterize the structural properties of the Hst54-15-Spd conjugates by performing atomistic molecular dynamics simulations in combination with small-angle X-ray scattering. It was shown that the Hst54-15-Spd conjugates adopt extended and slightly rigid random coil conformations without any secondary structure in aqueous solution. It is hypothesized that the increased fungal killing potential of Hst54-15-Spd, in comparison with the Spd-Hst54-15 conjugate, is due to the more extended conformations of the former, which cause the bonded Spd molecule to be more accessible for recognition by polyamine transporters in the cell.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Chemical Information and Modeling2005-01-01+01:00
volume
57
issue
6
pages
12 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85021285654
  • wos:000404422600011
ISSN
1549-9596
DOI
10.1021/acs.jcim.7b00150
language
English
LU publication?
yes
id
526808db-a963-4c2d-8e24-640499c9ae67
date added to LUP
2017-07-11 12:34:09
date last changed
2018-01-07 12:11:14
@article{526808db-a963-4c2d-8e24-640499c9ae67,
  abstract     = {<p>Histatin 5 (Hst5) is a naturally occurring antimicrobial peptide that acts as the first line of defense against oral candidiasis. It has been shown that conjugation of the active Hst5 fragment, Hst5<sub>4-15</sub>, and the polyamine spermidine (Spd) improves the candidacidal effect. Knowledge about the structure of these conjugates is, however, very limited. Thus, the aim of this study was to characterize the structural properties of the Hst5<sub>4-15</sub>-Spd conjugates by performing atomistic molecular dynamics simulations in combination with small-angle X-ray scattering. It was shown that the Hst5<sub>4-15</sub>-Spd conjugates adopt extended and slightly rigid random coil conformations without any secondary structure in aqueous solution. It is hypothesized that the increased fungal killing potential of Hst5<sub>4-15</sub>-Spd, in comparison with the Spd-Hst5<sub>4-15</sub> conjugate, is due to the more extended conformations of the former, which cause the bonded Spd molecule to be more accessible for recognition by polyamine transporters in the cell.</p>},
  author       = {Jephthah, Stephanie and Henriques, Joao and Cragnell, Carolina and Puri, Sumant and Edgerton, Mira and Skepö, Marie},
  issn         = {1549-9596},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1330--1341},
  publisher    = {The American Chemical Society},
  series       = {Journal of Chemical Information and Modeling2005-01-01+01:00},
  title        = {Structural Characterization of Histatin 5-Spermidine Conjugates : A Combined Experimental and Theoretical Study},
  url          = {http://dx.doi.org/10.1021/acs.jcim.7b00150},
  volume       = {57},
  year         = {2017},
}