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Protein & Peptide Letters
ISSN: 0929-8665
Protein & Peptide Letters
Volume 14, Number 6, 2007
Contents
Protein Peptide Informatics and Drug Designing
Guest Editor: Rajani R. Joshi
Editorial Pp. 507-508
R.R. Joshi
Comparative Kinomics of Plasmodium Organisms:
Unity in Diversity Pp. 509-517
K. Anamika and N. Srinivasan
[Abstract]
Statistics of Catalytic Domain Sequences in Protein
Kinases Vs Non-Kinases Pp. 518-527
R.R. Joshi and C. Manda
[Abstract]
Prediction of B Cell and T Cell Epitopes of DBLα
Domain in Plasmodium falciparum Malaria Vaccine Candidate
Var Gene Pp. 528-530
D. Ozarkar, D. Prakash, D.N. Deobagkar and D.D. Deobagkar
[Abstract]
Characterization of Antibody-Binding Sites on Proteins:
Development of a Knowledgebase and Its Applications in Improving
Epitope Prediction Pp. 531-535
A.D. Ghate, B.U. Bhagwat, S.G. Bhosle, S.M. Gadepalli
and U.D. Kulkarni-Kale
[Abstract]
Peptide Vaccine Models Using Statistical Data Mining
Pp. 536-542
R.R. Joshi
[Abstract]
Chimeric T Helper-B Cell Peptides Induce Protective
Response Against Japanese Encephalitis Virus in Mice
Pp. 543-551
S.S. Dewasthaly, G.S. Bhonde, V. Shankarraman, S.M. Biswas,
V.M. Ayachit and M.M. Gore
[Abstract]
Distribution of Tripeptides in MHC Binding Peptides
Pp. 552-556
S. Anishetty and G. Pennathur
[Abstract]
Interaction Profiling of T-Cell Epitopes with MHC-Class
I Molecules Pp. 557-564
B.P. Dash, S. Mukherjee, V.L. Suhas and N. Chandra
[Abstract]
X-Ray Structure of HIV-1 Protease Tethered Dimer Complexed
to Ritonavir Pp. 565-568
A. Das, D.R. Rao and M.V. Hosur
[Abstract]
Mapping Selectivity and Specificity of Active Site
of Plasmepsins from Plasmodium falciparum Using Molecular
Interaction Field Approach Pp. 569-574
A. Kumar and I. Ghosh
[Abstract]
Support Vector Machine Based Prediction of Glutathione
S Transferase Proteins Pp. 575-580
N.K. Mishra, M. Kumar and G.P.S. Raghava
[Abstract]
A Small Tripeptide AFA Undergoes Two-State Cooperative
Conformational Transitions: Implications for Conformational
Biases in Unfolded States Pp. 581-589
S. Patel, R. Tamini and Y.U. Sasidhar
[Abstract]
Molecular Dynamics Simulations of C-Terminal Decapeptide
of Gastrin-Releasing Peptide in DMPC Bilayers: Structure,
Stability and Orientation of the Peptide Hormone Within the
Bilayers Pp. 590-596
P. Prakash and R. Sankararamakrishnan
[Abstract]
Molecular Interactions of the Mitochondrial Tim12
Translocase Subunit Pp. 597-600
C. Baud, C. de Marcos-Lousa and K. Tokatlidis
[Abstract]
Length and Composition Analysis of the Cytoplasmic,
Transmembrane and Stem Regions of Human Golgi Glycosyltransferases
Pp. 601-609
R.Y. Patel and P.V. Balaji
[Abstract]
General Articles
Development of a Mimotope-Based Vaccine Against CD20
Antigen Pp. 610-614
M. Li, W. Han, Q. Zhang, X. Xue, Z. Wang and Y. Zhang
[Abstract]
Pigment Epithelium-Derived Factor (PEDF) Inhibits
Angiotensin II-Induced Smooth Muscle Cell Proliferation Through
Its Anti-Oxidative Properties Pp. 615-617
S.-i. Yamagishi, T. Matsui, K. Nakamura and T. Imaizumi
[Abstract]
Structural Preferences of Neuroprotective S14G-Humanin
Peptide Analyzed by Molecular Modeling and Circular Dichroism
Pp. 618-624
A. Rojo-Domínguez, G. Ramírez-Galicia, J.
Havel and L.H. Gutiérrez-González
[Abstract]
Abstracts
[Back to top]
Editorial
R.R. Joshi
Protein and Peptide Informatics offers enormous applications
in deciphering of the molecular basis of diseases and in the
discovery, design and delivery of biologically active and
medicinally effective molecules. The past few decades have
witnessed new horizons of research and a paradigm shift in
drug designing strategies and technology development with
promising achievements to leap ahead in the post-genomic era.
This special issue of “Protein Peptide Letters”
sketches a panorama of multi-dimensional research at the interface
of Protein Peptide Informatics and Drug Designing with special
focus on key approaches and innovative contributions emanated
from Bioinformatics and Computational Biology.
Protein Kinases (PK) are drug-targets for
treatment of several dreaded ailments including cancer and
are of fundamental importance in modeling optimal drug activities
because of their regulatory role in phosphorylation and ATP
hydrolysis and hence in many signal transduction pathways
in eukaryotes. Experimental studies of their catalytic reactions
and inhibition have been integral parts of modern pharmaceutical
research and development projects. The review paper by Ms.
Anamika and Prof. N. Srinivasan adds a valuable contribution
in this area. The bioinformatics and comparative analysis
of PK families, their catalytic sequences and structural domains
in two strains of Plasmodium presented here elucidate
the molecular pathways and growth kinetics of this protozoan
parasite which causes Malaria.
Statistical datamining of catalytic domain sequences of Protein
Kinases carried out in my computational lab (c.f.
paper by R. R. Joshi and Chaithanya M.) reveals some interesting
facets of ‘selective conservation’ and flexibility
of structural genomics of this special family of drug-targets.
In the past two decades, trend-setting initiatives have been
put forth to understand the biological and pathogenic properties
of the human T-cell stimulating viruses and suppressors and
T-cell and B-cell epitopes of microorganisms and other antigenic
carriers of diseases. Advancement of informatics of Immunogenetics
and cellular and molecular Immuno-interactions has boosted
emerging applications in anti-viral drug engineering
and vaccine discovery. Recent developments
focus upon peptide-drug design and computer aided vaccine
synthesis. Six papers in this special issue deal with multidimensional
research and development applications in this key area.
Ms A. D. Ozarkar and Profs. D Prakash, D. N. Deobagkar and
D. D. Deobagkar have analyzed the structure of the Duffy binding
like (DBLα)
domain in Plasmodium falciparum Malaria Vaccine candidate
var gene. Their predictions of likely T- and B- cell
epitopes in this domain provide interesting implications and
applications. A. D. Ghate, B. U. Bhagwat, S. B. Bhosle, S.
M. Gadepalli and U. D. Kulkarni-Kale report development of
a database and inference tools archiving molecular interactions
of protein antigen-antibody. They have also shown good applications
of this knowledgebase, named AgAbDb, in modifying the parameters
for etimation of B-cell epitopes.
Thorough exploration of experiment data and knowledgebase
requires mathematically or statistically sound algorithms.
My paper on sequential eptiope prediction presents a new,
computationally feasible and reliable algorithm of this sort
with promising applications in vaccine development by peptide
synthesis. The probabilistic model developed for this purpose
also computes the binding correspondence between the sequences
of predicted epitopes and complementarity determining
regions (CDRs) of antibodies and thus provides a possible
mode of interpreting the genomics of specificity and affinity
of antigen – antibody interactions.
Experimental investigations of S.S. Dewasthaly, G.S. Bhonde,
V.S. Raman, S. M. Biswas, V.M. Ayachit, and Dr. M.M. Gore
identify T-cell stimulating and MAb binding peptide epitopes
from envelope glycoprotein (Egp) and NS-1 and Mem proteins
of Japanese Encephalitis Virus in mice. Derived from these
results the authors report Chimeric T helper- B cell peptides
for effective vaccination.
Because of their key role in the process of immunity, the
Major Histocompatibility complex (MHC) and HLA (Human Leukocyte
Antigens) molecules are of extensive interest in drug designs.
Bioinformatics tools have boosted newer developments revolving
around MHC/HLA binding peptides. Drs. S.
Anishetty and P. Gautam delineate certain tri-peptide patterns
in MHC binding sequences and analyze their position specific
binding properties. Their results on distribution of rigid
tri-peptides reveal interesting possibilities for peptide-based
immuno modulators too. B.P. Dash, S. Mukherjee, V.L. Suhas,
and Dr. Nagasuma.Chandra focus at structural features of HLA-peptide
binding. Their paper contributes towards identifying critical
determinants of recognition by different alleles and is thus
of special use in investigating the structural genomics of
the T-cell receptors, which is important in gene-based drug
discovery and vaccine designing.
Structure Based Drug Design (SBDD) is most
prominent method of computer aided drug discovery and development.
It incorporates – (i) identifying three-dimensional
structure of proteins that would fit into a ligand binding
site to modulate certain functions; (ii) detecting specific
activity pockets or binding sites in a given or predicted
structure of ligands and/or receptor proteins of interest.
Determination or prediction of protein structures, demarcation
of their structural and functional domains, pattern recognition,
etc, which are building blocks of Structural Genomics and
Proteomics, constitute the core of SBDD as well. This special
issue brings a collection of state-of-the-art contributions
on these aspects. Some of the papers deal with prediction
and/or experimental analysis of structure and functions/binding-characteristics
of pharmaceutically important proteins, while
others present algorithms and databases which have wider applications
in classification and characterization of special features
of proteins and protein-protein and protein-ligand binding.
A high resolution X-ray structure of a complex between HIV-1
protease tethered dimer and ritonavir obtained by Drs. A.
Das, D. R. Rao and Prof. M.V. Hosur. As HIV-I protease is
a prominent target for design of drugs against Acquired Immuno
Deficiency Syndrome (AIDS). The identification of its inhibitor
sites and detailed atomic analysis presented in their paper
is an important addition to active research on suppressing
the killer virus.
The paper by Mr. A. Kumar and Prof. I. Ghosh, deals with a
hard problem of determining and distinguishing the selectivity
and specificity of Aspartic Proteases, which are sequentially
and structurally similar. The binding sites of some of these
enzymes in humans and in malarial parasite Plasmodium Falciparum
are characterized using molecular dynamics and interaction
mapping. As Plasmodium Falciparum is known to be resistant
to many of the existing medicines and as these enzymes (Plasmepsins
I to IV) are required in its metabolism, the results presented
here are of significant importance in design of new malarial
drugs against this principal causative agent of Malaria.
Support Vector Machines (SVM) are powerful datamining techniques,
extensively used in Bioinformatics applications. Dr. G. P.
S. Raghava and researchers N. Mishra and M. Kumar have applied
SVM to predict specific function of proteins from their sequences.
This is desired in annotation of genome sequences and also
in peptide or protein drug designs. Their paper focuses at
a particular class of proteins, viz, Glutathione S-transferases
(GST), which are vital in several in-vivo detoxification
reactions and stress survivability reactions.
Simulations of the molecular dynamics of protein folding require
optimal modeling and intensive high performance computing
to solve multidimensional, nonlinear energy minimization problems.
Interpretations of the simulation results provide insight
into Nature’s marvelous mechanism of producing sophisticated
functional units of life. Ms. S. Patel, R. Tamini and Prof.
YU Sasidhar have shown useful results on conformational transition
of tri-peptide AFA, which reveal possibility of selective
biases in the process of certain peptides folding into a stable
protein structure. The finding also acquires significance
noting that the state-of-the-art drug design methods often
use peptide mimic approach. Strong conformational preferences
in such small peptides would be useful in the peptidomimetic
derived drugs models and in peptide drugs or vaccines designs.
Because of their active roles in stimulating or inhibiting
membrane bound proteins, the G-proteins and GPCRs (G-Protein
Coupled Receptors) provide most attractive platform for drug
discovery and drug designing research. Ms. Priyanka P. and
Dr. R. Sankararamakrishnan have carried out molecular dynamics
simulation of Gastrin releasing peptide – GRP10 that
act on certain GPCRs and contribute to some crucial physiological
activities. This research paper elucidates several key features
of binding interactions of this biologically active dectapeptide.
The paper by Drs. C. Baud, C. de Marcos-Lousa and Prof. K.
Tokatlidis presents novel experimental research findings on
the native state and molecular interactions of a unique chaperon
(Tim12) that is localized in the inner mitochondrial membrane
and eases specific activations and biochemical ‘communications’
via hydrophobic precursors. Their analysis also offers valuable
information to explain insertion pathways of carrier proteins
in mitochondria and is therefore of notable relevance in understanding
the drug-transport and activity mechanisms at molecular levels.
The paper by Mr. R.Y. Patel and Prof. P. V. Balaji deciphers
the structural and functional features of cytoplasmic, transmembrane
and stem (CTS) regions of Golgi- glycosyltransferases (GlyT)
enzymes, which catalyze a wide range of glycosylation and
transglycosylation reactions. Thorough analyses of the length
and composition of these enzymes is presented taking into
account their substrate preferences in terms of their functional
roles in biosynthesis of blood group antigens, glycolipids,
N-glycans, O-glycans and glycosaminoglycans. Their results
elucidate yet unknown aspects of the topogenesis and actions
of these enzyme.
Bioinformatics tools developed for Gene/Peptide based or Structure
Based Drug Designing often offer wider applications in protein
structural genomics and proteomics. Novel research contributions
for such applications will be published in forthcoming issue
on the theme of the present one.
Rajani R. Joshi
Guest Editor
Protein & Peptide Letters
Professor, Department of Mathematics and
Associated Faculty (as Professor), School of Bioscience &
Bioengineering
Indian Institute of Technology Bombay, Powai
Mumbai 400076
India
Email: rrj@math.iitb.ac.in
[Back to top]
Comparative Kinomics of Plasmodium Organisms:
Unity in Diversity
K. Anamika and N. Srinivasan
Phosphorylation by protein kinases is a very common and crucial
process in many signal transduction pathways in eukaryotes.
This review describes comparative protein kinase analysis
of two apicomplexa Plasmodium falciparum (3D7 strain)
and Plasmodium yoelii yoelii (17XNL strain) which
are causative agents of malaria in human and African rat respectively.
Sensitive bioinformatics techniques enable identification
of 82 and 60 putative protein kinases in P. falciparum
and P. yoelii yoelii respectively and these sequences
could be classified into known subfamilies of protein kinases.
The most populated kinase subfamilies in both the plasmodium
species correspond to CAMK and CMGC groups. Analysis of domain
architectures enables detection of uncommon domain organization
in kinases of both the organisms such as kinase domain tethered
to EF hands as well as PH domain. Components of MAPK signaling
pathway is not well conserved in plasmodium organisms. Such
observations suggest that plasmodium protein kinases are highly
divergent from other eukaryotes. A transmembrane kinase with
6 membrane spanning segments in P. falciparum seems
to have no orthologue in P. yoelii yoelii. 19 P.
falciparum kinases have been found to cluster separately
from P. yoelii yoelii kinases and hence these kinases
are unique to P. falciparum genome. Only 28 orthologous
pairs of kinases seem to be present between these two plasmodium
organisms. Comparative kinome analysis of two plasmodium species
has thus provided clues to the function of many protein kinases
based upon their classification and domain organization and
also implicate marked differences even between two plasmodium
organisms.
[Back to top]
Statistics of Catalytic Domain Sequences in Protein
Kinases Vs Non-Kinases
R.R. Joshi and C. Manda
The catalytic regions of Protein Kinases are known to have
similarity in primary chains. However, it is not known whether
there is a signature profile specific to a particular
catalytic region? Whether the signature profile,
if any, is unique to a protein kinases family in a particular
species or in a group of species? We have attempted analyzing
some of these aspects by statistical data mining using an
authentic and exhaustive database of Protein Kinases. The
results reveal interesting features and provide some new directions
to look at their applications.
[Back to top]
Prediction of B Cell and T Cell Epitopes of DBLα
Domain in Plasmodium falciparum Malaria Vaccine Candidate
Var Gene
D. Ozarkar, D. Prakash, D.N. Deobagkar and D.D. Deobagkar
P. falciparum encodes PfEMP-1 which is important
in pathogenicity and virulence. We have analyzed the structure
of the Duffy binding like (DBLα)
domain of var genes and predicted the antigenic sites
and T and B cell epitopes which present a highly variable
picture with major implications in immune interactions and
vaccine design.
[Back to top]
Characterization of Antibody-Binding Sites on Proteins:
Development of a Knowledgebase and Its Applications in Improving
Epitope Prediction
A.D. Ghate, B.U. Bhagwat, S.G. Bhosle, S.M. Gadepalli
and U.D. Kulkarni-Kale
Immunoinformatics provides tools for reverse vaccinology and
encompasses development of knowledge bases and algorithms
for prediction of epitopes. AgAbDb, a database archiving molecular
interactions of antigen-antibody co-crystal structures, has
been developed (http://202.41.70.51:8080/agabdb2/). Analyses
of antibody-binding sites on proteins helped to fine-tune
the parameters for prediction of sequential and conformational
B-cell epitopes.
[Back to top]
Peptide Vaccine Models Using Statistical Data Mining
R.R. Joshi
Design and synthesis of peptide vaccines is of significant
pharmaceutical importance. A knowledge based statistical model
is fitted here for prediction of binding of an antigenic site
of a protein or a B-cell epitope on a CDR (complementarity
determining region) of an immunoglobulin. Linear analogues
of the 3D structure of the epitopes are computed
using this model. Extension for prediction of peptide epitopes
from the protein sequence alone is also presented. Validation
results show promising potential of this approach in computer-aided
peptide vaccine production. The computed probabilities of
binding also provide a pioneering approach for ab-initio
prediction of ‘potency’ of protein or peptide
vaccines modeled by this method.
[Back to top]
Chimeric T Helper-B Cell Peptides Induce Protective
Response Against Japanese Encephalitis Virus in Mice
S.S. Dewasthaly, G.S. Bhonde, V. Shankarraman, S.M. Biswas,
V.M. Ayachit and M.M. Gore
Virus neutralizing MAb binding and T helper cell stimulating
peptide epitopes from structural and non-structural proteins
of Japanese encephalitis virus were delineated. It was observed
that priming by T helper peptides potentiated neutralizing
antibody response against JE virus. Immunization with chimeric
T helper - B cell peptides could thus protect mice from lethal
challenge with JE virus.
[Back to top]
Distribution of Tripeptides in MHC Binding Peptides
S. Anishetty and G. Pennathur
Major Histocompatibility Complex (MHC) molecules are cell
surface glycoproteins that are central to the process of immunity.
MHC Class I and II molecules differ in their peptide binding
specificity. In this study we have analyzed a non redundant
set of MHC binding peptides derived from MHCPEP database,
in terms of tripeptides and their positional preference. Results
indicate that certain tripeptides have a preference to appear
at a particular position for a specific allele. Further, the
distribution of rigid tripeptides across all binding sequences
was also analyzed and their positions were correlated with
anchor residue positions.
[Back to top]
Interaction Profiling of T-Cell Epitopes with MHC-Class
I Molecules
B.P. Dash, S. Mukherjee, V.L. Suhas and N. Chandra
A key step in rational vaccine development is to understand
how antigens are recognized by their receptors. Several crystal
structures of MHC/HLA molecules are now available. We report
a structural bioinformatics study of peptide-HLA complexes
to derive features that generate recognition specificity,
useful for guiding the design process.
[Back to top]
X-Ray Structure of HIV-1 Protease Tethered Dimer Complexed
to Ritonavir
A. Das, D.R. Rao and M.V. Hosur
We report here the 2.5Å structure of HIV-1 protease
tethered-dimer ritonavir complex. The inhibitor bound in the
active site has different conformations in the two orientations.
There is only one hydrogen bond between the inhibitor and
the enzyme. The conserved flap-water is not found in the present
complex.
[Back to top]
Mapping Selectivity and Specificity of Active Site
of Plasmepsins from Plasmodium falciparum Using Molecular
Interaction Field Approach
A. Kumar and I. Ghosh
In the search for selectivity, the aspartic proteases are
known to be a very difficult case because the enzymes of this
family are not only sequentially but structurally also very
similar. To gain insight into the selectivity and specificity
of the aspartic proteases family we characterized the binding
sites of four malarial aspartic protease (plasmepsin I, plasmepsin
II, plasmepsin IV, P. vivax plasmepsin) and two human
aspartic proteases (cathepsin D and pepsin) with the intention
of identifying the regions that could be potential sites for
obtaining selectivity using molecular interaction field approach.
[Back to top]
Support Vector Machine Based Prediction of Glutathione
S Transferase Proteins
N.K. Mishra, M. Kumar and G.P.S. Raghava
Glutathione S-transferase (GST) proteins play vital role in
living organism that includes detoxification of exogenous
and endogenous chemicals, survivability during stress condition.
This paper describes a method developed for predicting GST
proteins. We have used a dataset of 107 GST and 107 non-GST
proteins for training and the performance of the method was
evaluated with five-fold cross-validation technique. First
a SVM based method has been developed using amino acid and
dipeptide composition and achieved the maximum accuracy of
91.59% and 95.79% respectively. In addition we developed a
SVM based method using tripeptide composition and achieved
maximum accuracy 97.66% which is better than accuracy achieved
by HMM based searching (96.26%). Based on above study a web-server
GSTPred has been developed (http://www.imtech.res.in/raghava/gstpred/).
[Back to top]
A Small Tripeptide AFA Undergoes Two-State Cooperative
Conformational Transitions: Implications for Conformational
Biases in Unfolded States
S. Patel, R. Tamini and Y.U. Sasidhar
It is important to understand the conformational biases that
are present in unfolded states to understand protein folding.
In this context, it is surprising that even a short tripeptide
like AFA samples folded/ordered conformation as demonstrated
recently by NMR experiments of the peptide in aqueous solution
at 280 K. In this paper, we present molecular dynamics simulation
of the peptide in explicit water using OPLS-AA/L all-atom
force field. The results are in overall agreement with NMR
results and provide some further insights. The peptide samples
turn and extended conformational forms corresponding to minima
in free energy landscape. Frequent transitions between the
minima are observed due to modest free energy barriers. The
turn conformation seems to be stabilized by hydrophobic interactions
and possibly by bridging water molecules between backbone
donors and acceptors. Thus the peptide does not sample conformations
randomly, but samples well defined conformations. The peptide
served as a model for folding-unfolding equilibrium in the
context of peptide folding. Further, implications for drug
design are also discussed.
[Back to top]
Molecular Dynamics Simulations of C-Terminal Decapeptide
of Gastrin-Releasing Peptide in DMPC Bilayers: Structure,
Stability and Orientation of the Peptide Hormone Within the
Bilayers
P. Prakash and R. Sankararamakrishnan
Gastrin-releasing peptide (GRP) is a member of bombesin-like
peptides and bombesin and neuromedin B are other members of
this family. They act on receptors that belong to the GPCR
superfamily and exert important physiological functions upon
binding to their receptors. The biologically active C-terminal
decapeptide of GRP (GRP10) was studied in explicit DMPC bilayers
using molecular dynamics simulations. In the initial conformation,
the peptide was placed per-pendicular to the membrane plane
and the peptide-membrane complex with ~20,000 atoms was simulated
for a period of 8 ns. After a 5 ns simulation, GRP10 adopted
a tilted orientation and the tilt angle with respect to the
bilayer normal was ~60º. Analysis of the interactions
of individual residues indicated the role of histidine residues
in maintaining a tilted orientation.
[Back to top]
Molecular Interactions of the Mitochondrial Tim12
Translocase Subunit
C. Baud, C. de Marcos-Lousa and K. Tokatlidis
The small Tims are chaperones that facilitate insertion of
hydrophobic precursors into the inner mitochondrial membrane.
We purified Tim12 and found it forms dimers that bind to Tim9.
In this interaction, Tim12 undergoes structural changes that
may be important for transport of its substrates in the mitochondrial
carrier import pathway.
[Back to top]
Length and Composition Analysis of the Cytoplasmic,
Transmembrane and Stem Regions of Human Golgi Glycosyltransferases
R.Y. Patel and P.V. Balaji
A dataset of experimentally characterized, human Golgi GlyTs
with type II membrane topology was created. Based on the experimentally
observed acceptor substrate preferences, the GlyTs were classified
into five functional categories: biosynthesis of blood group
antigens, glycolipids, N-glycans, O-glycans and glycosaminoglycans.
The cytoplasmic, transmembrane and stem (CTS) regions were
predicted and their length and composition were analyzed.
The stem region of GlyTs involved in the biosynthesis of glycolipids
and blood group antigens appear to have a shorter stem region
compared to those GlyTs which participate in the biosynthesis
of N- and O-linked glycans and glycosaminoglycans. The stem
regions of all the GlyTs, irrespective of the functional category
to which they belong, were found to be rich in disorder-promoting
amino acid residues. Thus, the stem region is largely devoid
of any regular secondary structure thereby facilitating its
tethering role. A higher frequency of occurrence of basic
amino acids is observed towards the N-terminus of the transmembrane
domain and this is suggested to be important for topogenesis
of these enzymes.
[Back to top]
Development of a Mimotope-Based Vaccine Against CD20
Antigen
M. Li, W. Han, Q. Zhang, X. Xue, Z. Wang and Y. Zhang
CD20, a B-cell-specific protein, is a primary target for immunotherapy
of B-cell lymphomas. We used a mimotopes of CD20 to construct
vaccines for B-cell-related disorders. The immunogenicity
of the vaccines was tested in BALB/c mice. Results of this
study suggest that the mimotope may be a useful tool for the
construction of a functional vaccine to treat B cell-related
disorders.
[Back to top]
Pigment Epithelium-Derived Factor (PEDF) Inhibits
Angiotensin II-Induced Smooth Muscle Cell Proliferation Through
Its Anti-Oxidative Properties
S.-i. Yamagishi, T. Matsui, K. Nakamura and T. Imaizumi
Pigment epithelium-derived factor (PEDF) is a potent inhibitor
of angiogenesis, suggesting that loss of this factor may be
involved in angiogenic eye disease. Here, we show that PEDF
inhibits angiotensin II-induced smooth muscle cell proliferation
through its anti-oxidative properties. Our present study suggests
that PEDF may play a protective role against atherosclerosis.
[Back to top]
Structural Preferences of Neuroprotective S14G-Humanin
Peptide Analyzed by Molecular Modeling and Circular Dichroism
A. Rojo-Domínguez, G. Ramírez-Galicia, J.
Havel and L.H. Gutiérrez-González
S14G-humanin (S14G-HN) is one of the latest of a new family
of neuropeptides with protective action against Alzheimer’s
disease insults. The structure of S14G-HN was studied with
both spectroscopic techniques and molecular dynamics simulation.
Secondary structure predictions and modeling of backbone conformation
were carried out. Side chain reconstruction, homology modeling
and molecular dynamics (MD) simulations were performed on
four different models. A beta strand tendency in residues
5 to 10 and a propensity to adopt turn or irregular conformation
in residues 13 to 17 was found. Circular dichroism experimental
studies of S14G-HN in aquaeous solution and in different 2,2,2-trifluoroethanol
(TFE) concentrations were also performed. In the absence of
TFE and at low TFE concentrations, CD spectra are indicative
of a small degree of ordering in the peptide. On further increment
of TFE concentration, changes occur that indicate the formation
of a structured conformation. Both experimental and computational
results indicate that S14G-HN has a reduced helical propensity,
in contrast with wild type humanin, as well as a higher conformational
flexibility.
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