Matejtschuk, Paul (1986) Structure and ligand-binding properties of abnormal human albumins. PhD thesis, University of Warwick.

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Abstract

Albumins Redhill, Warwick-1 and Carlisle are
monomeric slow albumin variants discovered in sera
obtained from patients in unrelated families resident
in the U.K.
Albumin Redhill had previously been studied in this
laboratory and was here purified by fast protein liquid
chromatrography (FPLC) and was subsequently submitted for
amino acid sequencing by the solid-phase Edman process.
It was found that Albumin Redhill has an extra N-terminal
arginine residue, and this places it into a new class
of albumin variants.
The binding of nickel and copper was studied in
greater depth than previously, and the binding of these
metal ions at the primary N-terminal site confirmed these
as being significantly inhibited due to the inclusion of
the extra basic amino acid residue. The binding of warfarin
to Albumin Redhill is reduced compared to normal albumin.
Albumin Carlisle, a heat-stable variant, was found
in three members of a family of English origin from
Carlisle. The binding of a range of dyes and the
electrophoretic mobility on a series of media were assessed.
The variant Albumin Carlisle was purified to homogeneity
by FPLC chromatofocusing and was shown to be antigenically
indistinguishable from albumin A, although it does have
a more basic isoelectric point (5.74 compared to 5.63 for
normal albumin). The evidence from both electrophoretic
and chromatographic procedures are consistent with an
acid
+
neutral amino acid mutation, and studies of the
CNBr fragments of the variant suggest that the site of
mutation is in the region 329-548 residues.
Reverse-phase HPLC has been used to pinpoint a
difference in the profile of the tryptic digest of the
variant albumin from the normal, and it may be that this
technique could be utilised to obtain molecular data on
the mutation.
The ligand binding properties of metal ions,
bilirubin, palmitate and warfarin were assessed and it
was shown that Albumin Carlisle has increased warfarin
binding but decreased bilirubin affinity, although
the binding of metal ions and palmitate was unaffected.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QD Chemistry Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	Albumins, Proteins, Ligand binding (Biochemistry)
Official Date:	1986
Dates:	Date Event 1986 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Hutchinson, D. W. (David Wesley)
Extent:	xxii, 307, [6] leaves : illustrations
Language:	eng

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