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Stability of HAMLET--A kinetically trapped {alpha}-lactalbumin oleic acid complex.

Fast, Jonas LU ; Mossberg, Anki LU ; Svanborg, Catharina LU and Linse, Sara LU (2005) In Protein Science 14(2). p.329-340
Abstract
The stability toward thermal and urea denaturation was measured for HAMLET (human -lactalbumin made lethal to tumor cells) and -lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than -lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15°C lower for apo HAMLET than for apo -lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost... (More)
The stability toward thermal and urea denaturation was measured for HAMLET (human -lactalbumin made lethal to tumor cells) and -lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than -lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15°C lower for apo HAMLET than for apo -lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than -lactalbumin, although it is a complex of -lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Protein Science
volume
14
issue
2
pages
329 - 340
publisher
The Protein Society
external identifiers
  • pmid:15659367
  • wos:000226626000006
  • scopus:13244274907
ISSN
1469-896X
DOI
10.1110/ps.04982905
language
English
LU publication?
yes
id
2897cfeb-6045-46b4-9621-32f0e692d87a (old id 133050)
date added to LUP
2007-06-29 09:44:34
date last changed
2017-07-02 03:29:17
@article{2897cfeb-6045-46b4-9621-32f0e692d87a,
  abstract     = {The stability toward thermal and urea denaturation was measured for HAMLET (human -lactalbumin made lethal to tumor cells) and -lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than -lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15°C lower for apo HAMLET than for apo -lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than -lactalbumin, although it is a complex of -lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.},
  author       = {Fast, Jonas and Mossberg, Anki and Svanborg, Catharina and Linse, Sara},
  issn         = {1469-896X},
  language     = {eng},
  number       = {2},
  pages        = {329--340},
  publisher    = {The Protein Society},
  series       = {Protein Science},
  title        = {Stability of HAMLET--A kinetically trapped {alpha}-lactalbumin oleic acid complex.},
  url          = {http://dx.doi.org/10.1110/ps.04982905},
  volume       = {14},
  year         = {2005},
}