Research Beyond the

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Research Beyond the Lipocalin Protein
Family Future Horizons
Dr Darren R Flower Edward Jenner Institute for
Vaccine Research
darren.flower_at_jenner.ac.uk
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FUNCTIONS
MULTIFUNCTIONAL and POORLY UNDERSTOOD
BIND SMALL MOLECULES BOUND BY CELL-SURFACE
RECPTORS FORM COMPLEXES WITH OTHER SOLUBLE
MACROMOLECULES
MANY FUNCTIONS retinol transport, phermone
transport, scavenging, immune functions, cell
regulation, cryptic coloration, siderophore
binding, heme interaction, etc. CONSEQUENTIAL
FUNCTIONS lipocalins are important diagnostic
markers for disease, many of the most important
mammalian aeroallergens are lipocalins, biotechnol
ogy applications, eg anticalins, etc.
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Sequence Diversity
Phyletic Diversity
MULTIFUNCTIONAL LIPOCALIN FAMILY
Ligand Diversity
Interaction Diversity
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CALYCIN PROTEIN SUPERFAMILY
Lipocalins FABPs, Avidins, MPIs, Triabin
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Dipeptidyl peptidase I (cathepsin C) exclusion
domain in rat human
Quinohemoprotein amine dehydrogenase Pseudomonas
bacteria
D-aminopeptidase avidin domain duplicated
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New Calycins (1)
YodA David G, Blondeau K, Schiltz M, Penel S,
Lewit-Bentley A. YodA from Escherichia coli is a
metal-binding, lipocalin-like protein. J Biol
Chem. 2003, epub.
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New Calycins (2)
Staphostatin B a cysteine protease
inhibitor. Filipek R, Rzychon M, Oleksy A, Gruca
M, Dubin A, Potempa J, Bochtler M. The
staphostatin-staphopain complex A forward
binding inhibitor in complex with its target
cysteine protease. J Biol Chem. 2003 Jul 21
R/K
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Lipocalin Receptors
Some receptors have been characterised
Megalin, Asialoglycoreceptor, CD45, LIMR
Kd / nM Receptor MW / kDa Megalin RBP 53
63 A1M 100 5x105-1x106 15-70 AGP 8.6
4x105-1x107 INS 17-40 8x107 185 OBP 2250
18.5pmol mg-1 BLG 26 1.2x1013
mg-1 51 PP14 6.7-28 9.5-36x104 Some data
also for MUP (), E-RABP, purpurin.
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CD45
Megalin
extracellular
intracellular
YWTD domain
LDL repeats
extracellular
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Chemical Characterisation
Kd
RL RL
k1, k-1
Find Protein -Protein Contact
HTS, MTS, VS, Pharmacophore Screening
Y2H, MicroArray, Proteomics, X- Linking, etc.
DRUG DESIGN
Functional Characterisation
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Where next for lipocalin research
I do not know but it will be fun finding out.