Current Projects
Biophysics and Physiological Function of Human Cytoglobin
Structure and Function of Non-Symbiotic Plant Haemoglobins
Metal Isotope and Magnetic Field Effects on Protein Kinases
Mechanisms of Acute Kidney Injury
Blood Substitutes
Haemoglobin Superfamily:
Pentacoordinate Globins:
A: Sperm Whale Myoglobin
B: Human Haemoglobin  chain
C: Yellow Lupin Leghemoglobin
Hexacoordinate Globins
D: Human Neuroglobin
E: Human Cytoglobin
F: Asian Rice
Non-Symbiotic Haemoglobin
Reeder, B.J. Antioxid. Redox. Sign. (2010) 13(7) 1088-1123
Interaction of Cytoglobin with lipids
changes structure of the protein
Various
Lipids
and
Lipid-like
molecules cause a change from 6 to
5 coordinate iron ligation state
Reeder, B.J., Svistunenko, D.A. & Wilson M.T.
“Lipid binding to cytoglobin leads to a change in
haem co-ordination: a role for cytoglobin in lipid
signalling of oxidative stress” Biochem. J. (2011)
434, 483–492
Stopped Flow
Laser Flash
EPR
What is the Mechanism of the
Cytoglobin Cell Protection?
Haemoglobins in Plants
Non-symbiotic plant haemoglobins (nsHbs)
Discovered from genomic sequencing in mid-90s.
Three classes of nsHbs:
Class 1 nsHb: related to leghaemoglobin, but with
hexacoordinate haem iron. Expressed in both roots
and rosette leaves. Forms stable O2 complex with
very high O2 affinity (Kd~2-10nM). Known structure
for rice and corn (but not Arabidopsis-until now).
Class 2 nsHb: Hexacoordinate globin ~60% sequence
homology to class 1 proteins. Lower O2 affinity
(Kd~150nM). Induced in rosette leaves at low
temperatures. Very high auto-oxidation rate. No
structures known.
Class 3 nsHb: Sequence suggests a truncated 2/2 αhelical structure like bacterial truncated Hb. Very
little information available. Very few papers. No
structures known.
Crystal Structure of A. thaliana Hb3
AHb3 Structure to
1.77 Å Resolution
Comparison of AHb3 structure (red) with
haemoglobin from Bacillus subtilis (blue)
Magnesium Isotope and Magnetic Field
Effects on Creatine Kinase Activity
Earthquakes and Acute Kidney Injury
The Spitak Earthquake (Armenia 1988) 25,000+ casualties
600-1000 survivors developed Rhabdomyolysis of which 225-385
developed Acute Kidney Injury (Acute Renal Failure).
Many fatalities due to inadequate renal treatment facilities (dialysis
machines)
In England up to 750,000 are effected by Acute Kidney Injury at a cost
of ~£600 million to NHS (5-25% due to rhabdomyolysis).
Blood Substitutes
Reeder, B.J., Grey, M., Silaghi-Dumitrescu, R., Svistunenko, D.A., Bülow, L., Cooper, C.E. &
Wilson, M.T “Tyrosine residues as redox cofactors in human hemoglobin: Implications
for engineering non toxic blood substitutes” J. Biol. Chem (2008) 283(45), 30780-30787
Can we Engineer a less toxic blood substitute?
Current/Developing Collaborations:
Cytoglobin:
Dr Dima Svistunenko (Essex)
Prof Geoff Moore (UEA)
Dr Marten Vos (Ecole, France)
Dr Philippe Laissue (Essex)
Dr Metodi Metodiev (Essex)
Plant Haemoglobin:
Dr Mike Hough (Essex)
Prof Leif Bulow (Lund, Sweden)
Prof Phil Mullineaux (Essex)
Dr Dima Svistunenko (Essex)
EMF:
Prof Mike Wilson (Essex)
Dr Gary Silkstone (Essex)
Prof Robert Hider (Kings C., London)
Acute Kidney injury:
Professor Kevin Moore, UCL
Prof Chris Cooper (Essex)
Prof L. Jackson Roberts II (Vanderbilt, USA)
Dr Sinan Battah (Essex/UCL)
Blood Substitutes:
Prof Chris Cooper (Essex)
Dr Gary Silkstone (Essex)
Prof Andrea Mozzarelli (Parma, Italy)
Prof Leif Bulow (Lund, Sweden)