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Protein
& Peptide Letters
ISSN: 0929-8665
Protein
& Peptide Letters
Volume 16, Number 8, 2009
Contents
Structural-Functional Studies of Animal
Toxins
Guest Editor: Marcos R.M. Fontes
Editorial Pp. 851
Influence of Quaternary Conformation on the Biological Activities
of the Asp49-Phospholipases A2s
from Snake Venoms Pp. 852-859
A.J. Magro, C.A.H. Fernandes, J.I. dos Santos
and M.R.M. Fontes
[Abstract] [Purchase
Article]
The Phospholipase A2
Homologues of Snake Venoms: Biological Activities and Their
Possible Adaptive Roles Pp. 860-876
B. Lomonte, Y. Angulo, M. Sasa and
J.M. Gutiérrez
[Abstract] [Purchase
Article]
Calcium-Independent Membrane Damage by
Venom Phospholipases A2
Pp. 877-886
A.H.C. de Oliveira, E.A. Aragão,
J.M. Sá, L. Chioato, R. Bugs- Bortoleto, R. Ruller,
T.L. Ferreira and R.J. Ward
[Abstract] [Purchase
Article]
The Intriguing Phospholipases A2
Homologues: Relevant Structural Features on Myotoxicity and
Catalytic Inactivity Pp. 887-893
J.I. dos Santos, C.A.H. Fernandes, A.J.
Magro and M.R.M. Fontes
[Abstract] [Purchase
Article]
Snake Venom Phospholipases A2:
A New Class of Antitumor Agents Pp. 894-898
R.S. Rodrigues, L.F.M. Izidoro, R.J. de
Oliveira Jr., A.M. Soares and V.M. Rodrigues
[Abstract] [Purchase
Article]
Structural and Pharmacological Features
of Phospholipases A2 from
Snake Venoms Pp. 899-907
R.C. de Paula, H.C. Castro, C.R. Rodrigues,
P.A. Melo and A.L. Fuly
[Abstract] [Purchase
Article]
Snake Venom L-amino Acid Oxidases: Some
Consideration about Their Functional Characterization
Pp. 908-912
J.P. Zuliani, A.M. Kayano, K.D. Zaqueo,
A.C. Neto, S.V. Sampaio, A.M. Soares and R.G. Stabeli
[Abstract] [Purchase
Article]
Venom-Sweet-Venom: N-Linked Glycosylation
in Snake Venom Toxins Pp. 913-919
S.G. Soares and L.L. Oliveira
[Abstract] [Purchase
Article]
Tityus serrulatus Scorpion Venom and
Toxins: An Overview Pp. 920-932
C.T. Cologna, S. Marcussi, J.R. Giglio, A.M.
Soares and E.C. Arantes
[Abstract] [Purchase
Article]
Brown Recluse Spider Venom: Proteomic
Analysis and Proposal of a Putative Mechanism of Action Pp.
933-943
L.D. dos Santos, N.B. Dias, J. Roberto. A.S.
Pinto and M.S. Palma
[Abstract] [Purchase
Article]
Pharmacological Perspectives of Wasp
Venom Pp. 944-952
M.C. Monteiro, P.R.T. Romão and A.M.
Soares
[Abstract] [Purchase
Article]
General Articles
Regular Papers
Structural Patterns in a Helices and β
Sheets in Globular Proteins Pp. 953-960
N. Bhattacharjee and P. Biswas
[Abstract] [Purchase
Article]
Identification of “Missing”
Metabolic Proteins of Plasmodium falciparum: A Bioinformatics
Approach Pp. 961-968
S. Mohanty and N. Srinivasan
[Abstract] [Purchase
Article]
Prediction of Small Molecules’
Metabolic Pathways Based on Functional Group Composition
Pp. 969-976
J. Lu, B. Niu, L. Liu, W.-C. Lu and
Y.-D. Cai
[Abstract] [Purchase
Article]
Improved Prediction of Lysine Acetylation
by Support Vector Machines Pp. 977-983
S. Li, H. Li, M. Li, Y. Shyr, L. Xie and
Y. Li
[Abstract] [Purchase
Article]
Identification of Ligand-Binding Pockets
in Proteins Using Residue Preference Methods Pp.
984-990
Z. Qiu and X. Wang
[Abstract] [Purchase
Article]
A Novel Physico-Chemical Property Based
Model for Studying the Effects of Mutation on the Aggregation
of Peptides Pp. 991-998
V.S. Mathura, D. Paris and M.J.
Mullan
[Abstract]
[Purchase Article]
Abstracts
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Editorial:
Animal venoms are a rich and complex mixture of toxic
and pharmacologically active proteins and peptides. Due to
this broad range of biological functions, these biomolecules
have been the subject of hundreds of scientific articles in
different research fields, including biochemistry, biophysics,
pharmacology, toxicology and medicine. This issue is focused
on the structural and functional aspects of some animal toxins
which could be important for understanding their biological
mechanisms and pharmacological properties.
In many rural areas in Asia, Latin American and Africa the
envenomation by snakes, scorpions, spiders and other venomous
animals causes thousands of deaths. This is a serious problem
of public health as a result of the associated chronic morbidity
(e.g., amputation, deformation and renal failure) causing
significant social and economic impact [1]. Even though the
patients are treated with anti-venom agents, many of them
present serious and permanent physical damage. The deeper
study of these compounds could be very important for the development
of new and more efficient treatments against animal venoms.
Additionally, the pharmacological properties of the peptides
and proteins from animal venoms lead to them being used as
effective drugs for hypertension, thrombosis and other diseases
and are potential drugs for a great variety of diseases including
cancer, Alzheimer’s, Parkinson’s and inflammatory
disorders.
This issue of Protein and Peptide Letters contains
eleven manuscripts describing structural and functional analysis
of different proteins and peptides from snakes, spiders, scorpions
and wasps. The first review by Magro and colleagues discusses
the importance of the oligomeric conformation of snake venoms
phospholipases A2 in their
biological function. The second review by Lomonte and co-workers
is focused in the Phospholipases A2
homologues from snake venoms, emphasizing their biological
activities in vivo and in vitro. The review
by Oliveira et al. is centered in Calcium-independent
membrane damage by snake venom Phospholipases A2
homologues. In the next article, dos Santos et al.
analyzed the controversial subject of the biological assembly
for Phospholipases A2 homologues
from snake venoms focused in the myotoxicity and catalytic
inactivity. Rodrigues et al. studied the snake venom
Phospholipases A2 as an antitumoral
agent while de Paula et al. reviewed snake venoms
from the pharmacological and structural perspective. The functional
and structural characteristics of snake venom L-amino acid
oxidades are reviewed by Zuliani et al. The review
by Soares and Oliveira is focused in the structure-function
relationship of the glycoproteins from snake venoms. Cologna
et al. presents a general revision of the pharmacological
and physiological proprieties of the venom from the most important
scorpion specie in South America. The review of dos Santos
and Dias et al. describe a proteomic analysis of
different proteins from Loxosceles intermedia spider
venom. In the last article, Monteiro et al. review
wasp venom components and their biological effects. Finally,
I hope this issue could have new and useful information about
different biological molecules from animal venoms.
REFERENCE
[1] Chippaux, J.P. Toxicon, 1998,
36, 1503.
Marcos R.M. Fontes
Guest Editor
Protein &
Peptide Letters
Dept. de Física e Biofísica
Instituto de Biociências
São Paulo State University – UNESP
Caixa Postal 510 – 18618-000
Botucatu – SP
Brazil
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Article]
Influence of Quaternary Conformation on the Biological Activities
of the Asp49-Phospholipases A2s
from Snake Venoms
A.J. Magro, C.A.H. Fernandes, J.I. dos Santos
and M.R.M. Fontes
One of the main components of snake venoms are the Asp49-phospholipases
A2, also known as svPLA2s.
The study of these toxins is a matter of great scientific
interest due to their wide variety of biological effects.
In this work we present strong evidences found in literature
and other aspects which strengthen the importance of quaternary
assembly for understanding the activities and molecular evolution
of svPLA2s.
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[Purchase
Article]
The Phospholipase A2
Homologues of Snake Venoms: Biological Activities and Their
Possible Adaptive Roles
B. Lomonte, Y. Angulo, M. Sasa and
J.M. Gutiérrez
A particular subgroup of toxins with phospholipase A2
(PLA2) structure, but devoid
of this enzymatic activity, is commonly found in the venoms
of snakes of the family Viperidae, and known as the PLA2
homologues. Among these, the most frequent type presents a
lysine residue at position 49 (Lys49), in substitution of
the otherwise conserved aspartate (Asp49) of catalytically-active
PLA2s. A brief and updated
overview of these toxic PLA2
homologues is presented, emphasizing their various biological
activities, both in vivo and in vitro. The
relevance of these bioactivities in relation to their possible
adaptive roles for the snakes is discussed. Finally, experiments
designed to assess the validity of such hypothetical roles
are suggested, to stimulate future studies in this field.
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Article]
Calcium-Independent Membrane Damage by Venom Phospholipases
A2
A.H.C. de Oliveira, E.A. Aragão,
J.M. Sá, L. Chioato, R. Bugs-Bortoleto, R. Ruller,
T.L. Ferreira and R.J. Ward
Many snake venom phospholipase A2s
(vPLA2s) present biological
effects that are independent of hydrolytic activity. Here
we review the evidence for the calcium-independent membrane
damaging activity of vPLA2s,
the possible relevance of this activity on their biological
effects, and models for the mechanism of membrane permeabilization
by these proteins.
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[Purchase
Article]
The Intriguing Phospholipases A2
Homologues: Relevant Structural Features on Myotoxicity and
Catalytic Inactivity
J.I. dos Santos, C.A.H. Fernandes, A.J. Magro and
M.R.M. Fontes
Phospholipases A2 homologues
are found in the venom of Crotalinae snakes, being their main
action related to myonecrosis induction. Although many studies
on these toxins had already been performed, their mechanism
of action remains unclear. Here, important aspects about these
toxins are reviewed, including their correct biological assembly
and how essential is the natural substitution D49K for their
catalytic inactivity.
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Article]
Snake Venom Phospholipases A2:
A New Class of Antitumor Agents
R.S. Rodrigues, L.F.M. Izidoro, R.J. de
Oliveira Jr., A.M. Soares and V.M. Rodrigues
Phospholipases A2 (PLA2)
are enzymes of high medical scientific interest due to their
involvement in a large number of human inflammatory diseases.
PLA2 constitute a diverse
family of enzymes which catalyses the hydrolysis of the sn-2
ester bond in glycerophospholipids and exhibit a wide range
of physiological and pathological effects. The ubiquitous
nature of PLA2 highlights
the important role they play in many biological processes,
as cell signaling and cell growth, including the generation
of proinflammatory lipid mediators such as prostaglandin and
leukotrienes, regulation of lipid mediators. The activity
and expression of several PLA2
isoforms are increased in several human cancers, suggesting
that these enzymes have a central role in both tumor development
and progression and can be targets for anti-cancer drugs.
On the other hand, some PLA2
isolated from Viperidae venoms are capable to induce antitumoral
activity. In summary PLA2
from snake venoms can be a new class of anticancer agents
and provide new molecular and biological insights of cancer
development.
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Structural and Pharmacological Features of Phospholipases
A2 from Snake Venoms
R.C. de Paula, H.C. Castro, C.R. Rodrigues,
P.A. Melo and A.L. Fuly
Phospholipases A2 enzymes
are found in many biological sources, including snake venoms.
Here we reviewed aspects of PLA2s
including biological and structural features, interaction
with binding receptors, inhibitors used on structure-function
relationship studies and highlighting the mechanism of action
and role of the snake venom PLA2s
products, the lysophosphatidylcholine.
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Article]
Snake Venom L-amino Acid Oxidases: Some Consideration about
Their Functional Characterization
J.P. Zuliani, A.M. Kayano, K.D. Zaqueo,
A.C. Neto, S.V. Sampaio, A.M. Soares and R.G. Stabeli
Snake Venom L-amino acid oxidases (LAAOs E.C. 1.4.3.2)
are flavoenzymes broadly found in various snake venom compositions.
LAAOs have become an attractive subject for molecular biology,
biochemistry, physiology and medicine due to their actions
on various cells and biological effects on platelets, apoptosis,
hemorrhage and others. In this review we try to summarize
some of these reports, with special emphasis on apoptosis,
anti-protozoa, bactericidal and anti-viral activities.
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Article]
Venom-Sweet-Venom: N-Linked Glycosylation in Snake
Venom Toxins
S.G. Soares and L.L. Oliveira
Protein glycosylation represents one of the most important
post-translational events, and is a mean of diversifying a
protein without recourse to the genome. The venoms produced
by snakes contain an abundance of glycoproteins with N-linked
carbohydrates. N-linked glycosylation can ensure
the correct folding of important functional domains. Characterization
of carbohydrates structures aids in development of human therapeutics
by snake venom toxins.
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[Purchase
Article]
Tityus serrulatus Scorpion Venom and Toxins: An Overview
C.T. Cologna, S. Marcussi, J.R. Giglio, A.M. Soares and
E.C. Arantes
Tityus serrulatus is considered the most dangerous scorpion
in South America and responsible for most of the fatal cases.
This review will focus on Tityus serrulatus scorpion
venom (Tsv), its long-chain Na+-channel
toxins (NaTx), which include α-
and β-neurotoxins,
short-chain K+-channel toxins
(KTx), hyaluronidase, proteases and other peptides hitherto
identified.
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Article]
Brown Recluse Spider Venom: Proteomic Analysis and Proposal
of a Putative Mechanism of Action
L.D. dos Santos, N.B. Dias, J. Roberto. A.S.
Pinto and M.S. Palma
Loxosceles intermedia spider venom was subjected
to proteomic analysis through a MudPIT shot-gun approach to
identify the protein composition. Were identified 39 proteins
which seem to responsible by the lesion of different types
of tissues, to some physiopathological actions and by the
prevention of structural damage to the toxin structures.
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Article]
Pharmacological Perspectives of Wasp Venom
M.C. Monteiro, P.R.T. Romão and A.M. Soares
Venoms of several animals have been used to study various
physiopathologic processes, and also to offer opportunity
to design and develop new therapeutic drugs. We briefly review
certain wasp venom components and their biological effects,
which may be potential sources of novel pharmacologically
active compounds.
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Structural Patterns in a Helices and β
Sheets in Globular Proteins
N. Bhattacharjee and P. Biswas
Secondary structural elements like α-helix
and β-sheet
constitute the major components of proteins. Here we present
a systematic position wise analysis of the structural and
sequence characteristics of alpha-helices and beta-sheets.
Helix and sheet are found to follow a complementary distribution
pattern along the protein chain length. We have calculated
the conformational parameters of the amino acids forming helices
and sheets. Other properties like hydrophobicity, temperature-factor
and relative entropy are found to be correlated with the distribution
pattern of these secondary struc-tures. This gives an insight
about the conservation or variation of the secondary structure
in proteins, which may have significant implications on de
novo protein design.
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Article]
Identification of “Missing” Metabolic Proteins
of Plasmodium falciparum: A Bioinformatics Approach
S. Mohanty and N. Srinivasan
The genome of Plasmodium falciparum, a malarial
parasite, is atypical as many of the encoded proteins have
diverged extensively from their homologues in other organisms.
Hence homology-based information transfer is not entirely
successful and presently, proper function annotation is unavailable
for over 50% of the proteome. It has been hypothesized that
enzymes participating in nearly 69 metabolic steps are not
yet identified. In this paper we report detection of some
of the “missing metabolic enzymes” of P. falciparum.
Our approach for remote homology detection to recognize the
“missing” P. falciparum enzymes employs
multiple profiles for every protein domain family. A blind
assessment of the approach to recognize known metabolic proteins
of P. falciparum resulted in 94% success rate. Using
this approach we have successfully recognized 14 of the “missing”
enzymes. Results of protein fold recognition and information
from microarray and protein-protein interaction datasets are
consistent with our predictions. In a few cases we also provide
the list of functionally important residues extrapolated on
the basis of homology.
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Prediction of Small Molecules’ Metabolic Pathways Based
on Functional Group Composition
J. Lu, B. Niu, L. Liu, W.-C. Lu and
Y.-D. Cai
How to correctly and efficiently determine small molecules’
biological function is a challenge and has a positive effect
on further metabonomics analysis. Here, we introduce a computational
approach to address this problem. The new approach is based
on AdaBoost method and featured by function group composition
to the metabolic pathway analysis, which can fast and automatically
map the small chemical molecules back to the possible metabolic
pathway that they belong to. As a result, jackknife cross
validation test and independent set test on the model reached
73.7% and 73.8%, respectively. It can be concluded that the
current approach is very promising for mapping some unknown
molecules’ possible metabolic pathway. An online predictor
developed by this research is available at http://chemdata.shu.edu.cn/pathway.
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Improved Prediction of Lysine Acetylation by Support Vector
Machines
S. Li, H. Li, M. Li, Y. Shyr, L. Xie and
Y. Li
Reversible acetylation on lysine residues, a crucial
post-translational modification (PTM) for both histone and
non-histone proteins, governs many central cellular processes.
Due to limited data and lack of a clear acetylation consensus
sequence, little research has focused on prediction of lysine
acetylation sites. Incorporating almost all currently available
lysine acetylation information, and using the support vector
machine (SVM) method along with coding schema for protein
sequence coupling patterns, we propose here a novel lysine
acetylation prediction algorithm: LysAcet. When compared with
other methods or existing tools, LysAcet is the best predictor
of lysine acetylation, with K-fold (5- and 10-) and jackknife
cross-validation accuracies of 75.89%, 76.73%, and 77.16%,
respectively. LysAcet’s superior predictive accuracy
is attributed primarily to the use of sequence coupling patterns,
which describe the relative position of two amino acids. LysAcet
contributes to the limited PTM prediction research on lysine
ε-acetylation,
and may serve as a complementary in-silicon approach for exploring
acetylation on proteomes. An online web server is freely available
at http://www.biosino.org/LysAcet/.
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Identification of Ligand-Binding Pockets in Proteins Using
Residue Preference Methods
Z. Qiu and X. Wang
Identification of ligand-binding pockets in proteins is pivotal
to protein function definition and drug discovery. In this
study, we focus on determining the binding pockets in proteins
for potential ligands without any a priori knowledge. Three
methods based upon residue preference concept are proposed
to predict ligand-binding pockets, where we deal with three
types of residue preference (residue based, atom based and
atom-contact-pair based preference), respectively. Two test
sets were chosen to examine the proposed methods. Two different
identification rules (named Top1 and Top2) are used to detect
ligand-binding pockets. The results show that the atom-contact-pair
method has good accuracy and high efficiency, better than
the other two methods. By means of preference analysis for
amino acids and atom-contact-pairs, we find that Gly and atom-contact-pairs
on aromatic residues appear at ligand-binding pockets more
frequently. The former favors pocket flexibility, and the
latter shows that aggregate hydrophobic surface may play an
important role in complex formation.
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A Novel Physico-Chemical Property Based Model for Studying
the Effects of Mutation on the Aggregation of Peptides
V.S. Mathura, D. Paris and M.J. Mullan
Macromolecular events like protein aggregation are complex
processes involving physico-chemical properties of their constituting
residues. In this study, we used 5-dimensional physico-chemical
property (PCP-descriptors) descriptors of amino acids, derived
from 237 physico-chemical properties, to develop linear (LM)
and neural network (NM) based regression models. We demonstrate
their prediction performance in log values of aggregation
rates (Ψ)
for 15 human muscle acyl-phosphatase (AcP) mutants. The correlation
coefficient between the predicted and the observed Ψ-values
of the point mutations by LM and NM was 0.81 (p-value<0.001)
and 0.71 (p-value<0.002)
respectively. Using LM, we calculated Ψ-values
for all possible mutations and performed an average linkage
cluster analysis. We identified three groups of amino acids
that differ in tolerance to mutations, resulting in increased
or decreased aggregation rates. We suggest that our linear
regression model can be applied to predict the aggregation
propensity of point mutants where only sequence information
is known. We also show that sequences containing beta-sheet
classes of Structural Classification of Proteins (SCOP) have
a higher propensity for aggregation.
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