International Journal of Drug Discovery, ISSN: 0975–4423, Volume 1, Issue 1, 2009, pp-14-17
Copyright © 2009, Bioinfo Publications, International Journal of Drug Discovery, ISSN: 0975–4423, Volume 1, Issue 1, 2009
Immunoproteomics approach for prediction of antigenic epitope of Tertiapin from Apis mellifera
Gomase V. S., Phadnis A. C. and Ghatak A.A.
Department of Bioinformatics, Padmashree Dr. D. Y. Patil University, Plot No-50, Sector-15, CBD
Belapur, Navi Mumbai, 400614, India, Mail- virusgene1@yahoo.co.in, Mobile- +91-9987770696,
www.bioinfo.in
Abstract –The bee venom is used for treating a wide variety of disease conditions. It has also been
found to be a strong immunological agent, stimulating the body's protective mechanisms against
disease. The major treatment is gene therapy or recombinant DNA vaccines involved targeting multiple
antigenic components to direct and empower the immune system to protect the host from infection.
Limitation of therapy to the treatment of patients suffering from various adverse reaction and
contraindications are always experienced. Tertiapin is a neurotoxin from the honeybee venom. It
interacts specifically with calmodulin in the presence of Ca2+. Antigenic epitopes on Tertiapin protein of
Apis mellifera (honey bee) is important determinants sites for protection against disorders. As our
knowledge of the immune responses to a protein antigen progressed, it became clear that the whole
protein is not necessary for raising the immune response, but small segments (NCNRIIIPHMCWK, 4-16)
of tertiapin protein called the antigenic determinants or the epitopes are sufficient for eliciting the desired
immune response. Immunization cassettes should be capable of immunizing of broad immunity against
both humoral and cellular epitope thus giving vaccines the maximum ability to deal with Tertiapin protein
of Apis mellifera immune escape. We have predicted a successful immunization strategy.
Keywords- Tertiapin, apitherapy, Antigenic epitope, Hydrophobicity, Hydrophilicity
Introduction
Apitherapy, or bee therapy, is the use of
products of the common honeybee for
therapeutic purposes. Honeybee venom, bee
pollen, raw honey, royal jelly, and propolis are
the products generally considered to have
medicinal effects. These products are said to
be effective against a wide range of ailments,
from arthritis and chronic pain to multiple
sclerosis and cancer, although few scientific
studies have as yet proved their benefits. Bee
venom is a potent anti-inflammatory
antioxidant, antifungal, antibacterial, and
possesses radioprotectant actions. It has been
found to exert powerful actions as an
antibacterial agent, anti-inflammatory,
antiarthritic, antirheumatic, in
neurodegenerative disease, as a cardiotonic,
an antioxidant, and as a diaphoretic and
diuretic. It has also been found to be a strong
immunological agent, stimulating the body's
protective mechanisms against disease. The
Eclectic Botanical physicians considered it to
be a potent alterative.
Tertiapin
Tertiapin is a neurotoxin from the honeybee
venom. It interacts specifically with calmodulin
in the presence of Ca2+. Miroshnikov, et al.
1983 was studied using calmodulin-cAMP
phosphodiesterase system. Tertiapin does not
affect the unstimulated basal activity of
phosphodiesterase. However, it totally inhibits
the enzyme-activating capacity of calmodulin.
Analysis of the dose-dependent activation of
phosphodiesterase by calmodulin in the
presence of tertiapin indicated that inhibition is
caused by the interaction of two tertiapin
molecules with calmodulin (Kd 2 microM). The
data obtained suggest that the toxic effect of
tertiapin in nervous tissue is mediated by
blockade of calmodulin function [1].
The cells contain phosphodiesterase of two
types. One of them possesses a high affinity for
cyclic AMP. The cell regulation is
phosphodiesterase with low affinity for the
substrate and its activity is modulated by the
calmodulin-Ca2+ complex, cyclic GMP and
NAD+ at micromolar concentrations. The effect
on the phosphodiesterase system of a "quick"
messenger, Ca2+ and "slow" messengers,
cyclic GMP and NAD+, has the same
consequences. The functional significance of
such an activity modulation may be the
necessity to maintain the conditions for
phosphodiesterase functioning when Km much
greater than cyclic AMP and the reaction rate
are directly proportional to the substrate
concentration. Studies of PC-12 cells revealed
a chronic effect of phosphodiesterase activity
change under the action of staphylococcal
enterotoxin A. This protein induces
differentiation of PC-12 cells and possesses a
NAD+-glycohydrolase activity. As a result, the
enzyme activity falls, cyclic AMP level
increases and cell differentiation starts. The
activity of soluble phosphodiesterase of PC-12
cells also decreases under the effect of two
neurotoxins from bee venom, melittin and
tertiapin. Both the toxins at concentration of 10
microM completely block calcium regulation of
the enzyme. Inhibition of Ca2+ action is
achieved as the result of the activated
calmodulin molecule [2]. Tertiapin is a small
protein derived from honeybee venom. It
inhibits the GIRK1/4 and ROMK1 channels with
nanomolar affinities. Methionine residue 13 in
TPN interacts with residue F148 in the channel,
located just outside of the narrow region of the
ROMK1 pore [3]. A recent study indicated that
tertiapin is a potent blocker of certain types of
inwardly rectifying K (+) (Kir) channels.
Tertiapin fully inhibited acetylcholine (1
microM)-induced muscarinic K (+) (K(ACh))
channel currents in atrial myocytes. At the
single-channel level, tertiapin inhibited the