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Protein
& Peptide Letters
ISSN: 0929-8665
Protein
& Peptide Letters
Volume 17, Number 2, 2010
Contents
Regular Papers
Identification of the Amino Acid Residues Affecting
the Catalytic Pocket of the Sulfolobus solfataricus
Signature Amidase Pp. 146-150
Cilia Elisa and Ammendola Sergio
[Abstract] [Purchase
Article]
Interaction and Structural Modification of Topoisomerase
IIα
by Peptidyl Prolyl Isomerase, pin1: An In Silico
Study Pp. 151-163
Rohit Mathur, Shubhanker Suman, Nicolas Beaume, Mashook Ali,
Anant N. Bhatt, Madhu Chopra, Daman Saluja, Anil K. Mishra,
Sudhir Chandna, Pramesh N. Kapoor and Bilikere S.
Dwarakanath
[Abstract] [Purchase
Article]
Evaluation of Synthetic Cell-Penetrating Peptides,
Pro-Rich Peptide and Octaargine Derivatives, as Adenovirus
Vector Carrier Pp. 164-167
Shinya Kida, Yusuke Eto, Yasuo Yoshioka, Shinsaku Nakagawa,
Koichi Kawasakia and Mitsuko Maeda
[Abstract] [Purchase
Article]
Characterization of Chemical Modification of Tryptophan
by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
Pp. 168-171
C. Sivakama Sundari, K. Chakraborty, R. Nagaraj and
M.V. Jagannadham
[Abstract] [Purchase
Article]
Effect of Protein Concentration and pH on the Chitinase
Activity of Tapes japonica Lysozyme Pp.
172-175
Takashi Gotoa, Yoshito Abe, Taiji Imoto and Tadashi
Ueda
[Abstract] [Purchase
Article] [PMID:
19807675 PubMed - indexed for MEDLINE]
Evidence for the Binding of Phosphate Ion to the C-Terminus
Region in Aβ1-40
Using Heteronuclear NMR Analyses Pp. 176-180
Makiko Nagata-Uchiyama, Yoshito Abea, Akira Monjib, Shigenobu
Kanba and Tadashi Ueda
[Abstract] [Purchase
Article]
Efficient Expression of Aquaporin Z in Escherichia
coli Cell-Free System Using Different Fusion Vectors
Pp. 181-185
Zhinan Xu, Jiazhang Lian and Jin Cai
[Abstract] [Purchase
Article]
TNF-α
and Ghrelin: Opposite Effects on Immune System, Metabolism
and Mental Health Pp. 186-196
Hubertus Himmerich and Abigail J. Sheldrick
[Abstract] [Purchase
Article]
Kinetic and Conformational Studies of Adenosine Deaminase
Upon Interaction with Oxazepam and Lorazepam Pp.
197-205
A.A. Moosavi-Movahedi, H. Sepassi Tehrani, M. Amanlou,
M.N. Soltani Rad, G.H. Hakimelahi , F.-Y. Tsai, G. Ataie,
A.A. Saboury, F. Ahmad, A. Khalafi-Nezhad, N. Poursasan and
A. Sharifizadeh
[Abstract] [Purchase
Article]
Molecular Modeling of Human BAD, a Pro-Apoptotic Bcl-2
Family Member, Integrating Glycolysis and Apoptosis Pp.
206-220
Jie Yang
[Abstract] [Purchase
Article] [PMID:
19508210 PubMed - indexed for MEDLINE]
Purification and Characterization of a Lectin from
the Indian Cultivar of French Bean Seeds Pp. 221-227
A. Sharma, Jack H. Wong, Peng Lin, Y.S. Chan and T.B.
Ng
[Abstract] [Purchase
Article]
New Au (III), Pt (II) and Pd (II) Complexes with Pentapeptide
Glycyl-glycyl-L-Methyonyl-Glycyl-Glycine
and Their Interaction with Calf Thymus DNA Pp. 228-
237
A. Chapkanov, Y. Miteva, T. Kolev, M. Spiteller and
B. Koleva
[Abstract] [Purchase
Article] [PMID:
19508228 PubMed - indexed for MEDLINE]
Truncated Human Cathepsin L, Encoded by a Novel Splice Variant,
Exhibits Altered Subcellular Localization and Cytotoxicity
Pp. 238-245
P. Sansanwal, A.A. Shukla, T.K. Das and S.S.
Chauhan
[Abstract] [Purchase
Article] [PMID:
19663777 PubMed - indexed for MEDLINE]
Applying Chemometrics Approaches to Model and
Predict the Binding Affinities Between the Human Amphiphysin
SH3 Domain and Its Peptide Ligands Pp. 246-253
L. Liu, D. He, S. Yang and Y. Xu
[Abstract] [Purchase
Article]
Structural Homologies, Importance for Catalysis
and Lipid Binding of the N-Terminal Peptide of a Fungal and
a Pancreatic Lipase Pp. 254-259
F. Frikha, N. Miled, A.B. Bacha, H. Mejdoub and
Y. Gargouri
[Abstract] [Purchase
Article]
Copper (II) - HisAibGly Complex and
Its Superoxide Dismutase Activity Pp. 260-268
R.K. Singh, S. Prasad and U.P. Singh
[Abstract] [Purchase
Article]
Toward the Virtual Screening of Potential Drugs
in the Homology Modeled NAD+
Dependent DNA Ligase from Mycobacterium tuberculosis
Pp. 269-276
V. Singh and P. Somvanshi
[Abstract] [Purchase
Article]
Abstracts
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Identification of the Amino Acid Residues Affecting
the Catalytic Pocket of the Sulfolobus solfataricus
Signature Amidase
Cilia Elisa and Ammendola Sergio
36 mutants of the Sulfolobus solfataricus amidase
were analyzed by comparing biochemical data to structural
data obtained by a learning machine. The analysis shows that
beside well known catalytic residues, amino acid residues
Arg197, Lys209 and Asp228 are important for the catalytic
activity of the signature thermophilic amidase.
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Article]
Interaction and Structural Modification of Topoisomerase
IIα
by Peptidyl Prolyl Isomerase, pin1: An In Silico
Study
Rohit Mathur, Shubhanker Suman, Nicolas Beaume, Mashook Ali,
Anant N. Bhatt, Madhu Chopra, Daman Saluja, Anil K. Mishra,
Sudhir Chandna, Pramesh N. Kapoor and Bilikere S.
Dwarakanath
The peptidyl prolyl isomerase (Pin1) that catalyzes the isomerization
of peptide bonds involving proline and phosphorylated serine/threonine/tyrosine
and alters the conformation and differential folding has been
implicated in the regulation and function of phosphorylated
proteins including mitotic and cell cycle proteins viz.
Cdc25c, Bcl2, p53 etc. DNA topoisomerase IIα
is one of the nuclear enzymes that maintain the DNA topology
and regulates nuclear transactions like chromatin segregation
and mitosis. In the present studies, we have carried out in-silico
investigations on the possibilities of pin1 interaction with
topo IIa and its functional regulation. We found ten potential
pin1 interacting sites within topo IIα,
which were part of loop and/or low complexity regions except
helix at S802 within the catalytic domain. Proline directed
phosphorylation was found to be possible at 1354, 1361, 1393
positions by cdk. Change in dihedral angle (ω)
to 0 degree at all potential pin1 interacting sites at 575,
602, 802 and 950 for cis conformation of peptide bond introduced
significant structural change with higher potential energy.
All-cis-topo IIα
structure reveals that potential pin1 sites come closer to
each other, perhaps forming a motif, thereby suggesting cooperative
phenomenon to maintain higher potential energy conformation.
The bio-informatic analysis of topo IIα
showed that multisite interaction of pin1 is possible at all
the predicted sites. However, a strong possibility of pin1
interaction exist within c-terminal at 1213, 1247, 1354, 1361,
1393 sites, which may lead to either alterations in localization
or modification in the activity and perhaps stability of the
enzyme.
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Evaluation of Synthetic Cell-Penetrating Peptides,
Pro-Rich Peptide and Octaargine Derivatives, as Adenovirus
Vector Carrier
Shinya Kida, Yusuke Eto, Yasuo Yoshioka, Shinsaku Nakagawa,
Koichi Kawasakia and Mitsuko Maeda
Two cell-penetrating peptides, a Pro-rich peptide derivative,
acetyl-(Val-Arg-Leu-Pro-Pro-Pro)3-Gly-Cys
amide, and an octaarginine derivative, acetyl-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Gly-Cys
amide, were prepared by the solid phase method. Each peptide
was coupled to the heterobifunctional cross-linking reagent,
6-maleimidohexanoic acid N-hydroxysuccinimide ester,
and then conjugated to the Adenovirus vector containing luciferase
gene. Peptide-modified Ad, as compared with wild-type Ad,
exhibited excellent luciferase activity in B16BL6 cells.
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Characterization of Chemical Modification of Tryptophan
by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
C. Sivakama Sundari, K. Chakraborty, R. Nagaraj and
M.V. Jagannadham
Tert- butylation of tryptophan (2', 5', 7'- tri tertiary
butyl tryptophan), formed during acidolytic cleavage of synthetic
peptides Ac-KLVYWAE-CONH2
(A-YW) and Ac-KLVWWAE-CONH2
(A-WW), that are analogs of the fragment of Alzheimer’s
β-amyloid
peptide Ac-KLVFFAE-CONH2,
during solid-phase peptide synthesis, was characterized by
matrix-assisted laser desorption/ionization time of flight/time
of flight (MALDI TOF/TOF) mass spectrometry. Crude peptide
was fractionated by high performance liquid chromatography.
Peptide fractions were sequenced and modified tryptophan was
determined with the help of MALDI TOF/TOF mass spectra. Thus,
it is possible to pinpoint the particular tryptophan residue
that undergoes modification during synthesis of peptides containing
multiple tryptophan residues.
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[Purchase
Article] [PMID:
19807675 PubMed - indexed for MEDLINE]
Effect of Protein Concentration and pH on the Chitinase
Activity of Tapes japonica Lysozyme
Takashi Gotoa, Yoshito Abe, Taiji Imoto and Tadashi
Ueda
Tapes japonica lysozyme (TJL), which belongs to the
invertebrate-type lysozyme family, has a unique dimer formation.
The residues, which include catalytic residues (glutamate
18 and aspartate 30), at the dimer interface form electrostatic
interactions. Our previous study suggested that increasing
the NaCl concentration switched TJL from a dimer to monomer
structure, which increased TJL activity. Therefore, conversion
from the dimeric to the monomeric structure is crucial for
the TJL activity. In the present study, to further understand
the effect of NaCl on TJL dimer formation, we examined the
protein concentration and pH dependence of TJL activity in
the presence or absence of 500 mM NaCl. TJL activity was suppressed
at the high protein concentration. And the optimum pH of TJL
activity was decreased in the absence of NaCl. These dependencies
confirm the presence of electrostatic interactions between
molecules of TJL in the dimeric form in an aqueous solution.
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Evidence for the Binding of Phosphate Ion to the C-Terminus
Region in Aβ1-40
Using Heteronuclear NMR Analyses
Makiko Nagata-Uchiyama, Yoshito Abea, Akira Monjib, Shigenobu
Kanba and Tadashi Ueda
Amyloid fibril formation of amyloid beta peptide 1-40
(Aβ
1-40) was reported to be retarded in the presence of 150mM
phosphate buffer at pH 7 [Monji, Ustumi, Ueda, Imoto, Yoshida,
Hashioka, Tashiro and Tashiro, J. Neurochemistry,
77, 1425-1432 (2007)]. In order to elucidate
the reason why phosphate ion retards the amyloid fibril formation,
we examined the preferential binding sites of phosphate ion
to Aβ
1-40 using chemical shift perturbation analysis of heteronuclear
NMR. In titration analysis of 15N-labeled
Aβ1-40
in the presence of 150 mM phosphate ion or 150 mM chloride
ion, we identified the residues affected by these ions in
Aβ
1-40. As a result, we found the tendency that phosphate ion
preferentially bound to some residues located on the C-terminus
region where the region was reported to be the potential β-strand
region in Aβ1-40.
Therefore, we suggested that phosphate ions interacted with
the potential β-strand
region in Aβ1-40
to be hard to form β-sheet
in Aβ
1-40, resulting in retardation of the amyloid fibril formation.
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Efficient Expression of Aquaporin Z in Escherichia
coli Cell-Free System Using Different Fusion Vectors
Zhinan Xu, Jiazhang Lian and Jin Cai
Aquaporin Z (AqpZ) is a typical orthodox aquaporin with 6
transmembrane domains and five connecting loops. In order
to express this complex membrane protein efficiently, E.
coli cell-free expression system was employed as an alternative
to produce aquaporin Z. Using different fusion vectors containing
AqpZ gene, the expression level of fusion proteins in cell-free
system varied from 7.97 to 578.35 μg/ml,
while 7.34 to 340.81 μg/ml
for target protein (AqpZ). The free energy of mRNA secondary
structure at translation initiation region (TIR) was predicted
and demonstrated a positive relationship with the expression
level of AqpZ in cell-free system. This is the first report
of expressing water channel protein in E. coli cell-free
system, which has become a highly promising tool for fast
and efficient production of integral membrane proteins.
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TNF-α
and Ghrelin: Opposite Effects on Immune System, Metabolism
and Mental Health
Hubertus Himmerich and Abigail J. Sheldrick
Tumor necrosis factor-a (TNF-α)
is a glycoprotein hormone with important functions in inflammation
and apoptosis. It plays a significant role as a pro-inflammatory
cytokine in the defense against viral, bacterial and parasitic
infections and autoimmune disorders. Furthermore, it influences
energy homeostasis and has an anorexigenic effect on the hypothalamus.
TNF-α
has also been shown to be involved in the pathogenesis of
psychiatric disorders such as depression or narcolepsy.
Ghrelin is a peptide hormone which primarily regulates eating
behavior through modulation of expression of orexigenic peptides
in the hypothalamus. Ghrelin administration increases food
intake and body weight, while weight loss in turn increases
ghrelin levels. Secondly, it posesses anti-inflammatory properties.
It also seems to have an impact on mental health as it is
has been suggested to have antidepressant and anxiolytic properties.
Therefore, TNF-α
and ghrelin seem to have opposite effects regarding the hypothalamic
regulation of eating behavior, modulation of the immune response
and the state of mental health.
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Kinetic and Conformational Studies of Adenosine Deaminase
Upon Interaction with Oxazepam and Lorazepam
A.A. Moosavi-Movahedi, H. Sepassi Tehrani, M. Amanlou,
M.N. Soltani Rad, G.H. Hakimelahi , F.-Y. Tsai, G. Ataie,
A.A. Saboury, F. Ahmad, A. Khalafi-Nezhad, N. Poursasan and
A. Sharifizadeh
Oxazepam and lorazepam inhibit the adenosine deaminase (ADA)
differently. In the case of lorazepam temperature increment
causes an increase in the inhibition potency whereas higher
temperature reduces the inhibitory effect of oxazepam; which
proposes the overall profounder structural changes in the
case of lorazepam relative to those caused by oxazepam.
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[Purchase
Article] [PMID:
19508210 PubMed - indexed for MEDLINE]
Molecular Modeling of Human BAD, a Pro-Apoptotic Bcl-2
Family Member, Integrating Glycolysis and Apoptosis
Jie Yang
Comparison between the BAD complexes indicated that BAD all
docks a hydrophobic surface of PKAc regardless of its phosphorylation.
PKAc may prevent Bcl-xL from rebinding to BAD by phosphorylating
human BAD at Ser118; whereas human BAD is phosphorylated on
Ser75 in a BAD-Bcl-xL complex, resulting in the dissociation
of BAD.
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Article]
Purification and Characterization of a Lectin from
the Indian Cultivar of French Bean Seeds
A. Sharma, Jack H. Wong, Peng Lin, Y.S. Chan and T.B.
Ng
A lectin specific for glucuronic acid and galacturonic acid
has been isolated from seeds of the French bean Phaseolus
vulgaris using a procedure that involved affinity chromatography
on Affigel blue gel, fast protein liquid chromatography (FPLC)-ion
exchange chromatography on Mono S, and FPLC-gel filtration
on Superdex 200. The lectin was comprised of two 32-kDa subunits
with substantial N-terminal sequence similarity to other Phaseolus
lectins. The hemagglutinating activity of the lectin was stable
within the pH range of 1-13 and the temperature range of 10-60
°C. The lectin neither exhibited any antiproliferative
activity against tumor cells nor stimulated nitric oxide production
by murine peritoneal macrophages at doses as high as 1mM ,
The lectin failed to evoke any mitogenic response from murine
splenocytes as measured by [3H-methyl]-thymidine
incorporation and did not inhibit the activity of HIV-1 reverse
transcriptase. The lectin had no antifungal activity.
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[Purchase
Article] [PMID:
19508228 PubMed - indexed for MEDLINE]
New Au (III), Pt (II) and Pd (II) Complexes with Pentapeptide
Glycyl-glycyl-L-Methyonyl-Glycyl-Glycine
and Their Interaction with Calf Thymus DNA
A. Chapkanov, Y. Miteva, T. Kolev, M. Spiteller and
B. Koleva
The three new Au (III), Pt (II) and Pd (II) complexes
with pentapeptide glycyl-glycyl-L-methyonyl-glycyl-glycine
have been synthesized, isolated, and spectroscopically and
structurally elucidated in solution and in the solid-state.
Solid-state linear-dichroic infrared (IR-LD) spectroscopy
of oriented colloids in a nematic liquid crystal host, 1H-
and 13C-NMR, TGA and DSC,
UV-VIS spectroscopy, EPR, ESI- and FAB- mass spectrometry
and HPLC tandem mass spectrometry (HPLC-MS/MS) have been used.
Quantum chemical calculations and molecular modelling were
carried out in order to determine the structures and spectroscopic
properties of the ligand, the newly synthesised metal complexes
and their interactions with calf thymus DNA. The
pentapeptide coordinates in a tetradentate manner with the
metal ions via an S-atom on the methyonyl-side chain,
two N-amide nitrogens, (after a deprotonation of gly1
and gly2 residues)
and the primary NH2 nitrogen
of Nterminai. The MN3S chromophores
are distorted to near square planar geometry. Their interaction
with calf thymus DNA shows the competitive N7 (G) coordination
position, where the pentapeptide residues is coordinated with
the metal centers in a tridentate manner through the S- atom
and both N-amide centers. This interaction leads to a transfer
from a distorted square planar geometry (D4h
symmetry) to a pseudo tetrahedral (Td
symmetry) of the metal ions with the obtained dihedral angle
values of the MN3N7(G) chromophors
within 114.67° to 110.92°. The isolated Au (III) complex
is stable for about 1.5 months, while the stability of the
Au (III) complex/DNA adduct is decreased to 33 days.
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[Purchase
Article] [PMID:
19663777 PubMed - indexed for MEDLINE]
Truncated Human Cathepsin L, Encoded by a Novel Splice Variant,
Exhibits Altered Subcellular Localization and Cytotoxicity
P. Sansanwal, A.A. Shukla, T.K. Das and S.S.
Chauhan
Cathepsin L (ctsl), a lysosomal cyteine protease over
expressed and secreted by cancer cells, has been implicated
in a number of physiological and pathological processes including
tumor cell proliferation and metastasis. In the present study
we demonstrate that an unknown mRNA of human origin (Gene
Bank accession number AF 217997) is a splice variant of human
cathepsin L mRNA (hCATL A IV) and encodes a truncated form
of cathepsin L (Δctsl) containing only 151 C-terminal
amino acids. This isoform is cytotoxic to the mammalian cells.
Transient transfection studies revealed that unlike ctsl,
upon over expression in eukaryotic cells Δctsl is not
secreted in to the media. Immunogold electron microscopy revealed
its localization to nuclear, perinuclear and cytosolic regions.
In view of its cytotoxic property, targeted expression of
Δctsl in tumor cells may prove useful in the management
of cancer.
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Applying Chemometrics Approaches to Model and
Predict the Binding Affinities Between the Human Amphiphysin
SH3 Domain and Its Peptide Ligands
L. Liu, D. He, S. Yang and Y. Xu
In this study, we used two categories of molecular descriptors
as CODESSA and DPPS (divided physicochemical property scores
of amino acids) to parameterize structural characteristics
of 2015 human amphiphysin SH3 domain-binding decapeptides
at atom and residue levels. Based upon that, several robust
quantitative structure-affinity relationship (QSAR) models
were then constructed using partial least squares regression
(PLS) and least squares-support vector machine (LSSVM) coupled
with genetic algorithm (GA)-variable selection. Results show
that (1) GA is a powerful tool for variable selection by which
the most informative variable combinations can be efficiently
determined for PLS and LSSVM modeling, (2) regression models
constructed using nonlinear LSSVM approach are more robust
and predictable than those by linear PLS method, (3) the residue
level descriptor (DPPS) performs better in capturing peptide
structural characteristics, more amenable than those from
the atom level descriptor (CODESSA). By investigating the
optimal DPPS-based GA-LSSVM model, it is indicated that the
core motif of SH3 domain-binding peptides contributes significantly
to the binding affinity, whereas the two end residues, especially
the N-terminal residue, have a little effect on the binding
process.
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Structural Homologies, Importance for Catalysis
and Lipid Binding of the N-Terminal Peptide of a Fungal and
a Pancreatic Lipase
F. Frikha, N. Miled, A.B. Bacha, H. Mejdoub and
Y. Gargouri
Lipases share an overall α/β
hydrolase fold structure characteristic of serine hydrolases.
Nevertheless, each lipases group possesses its characteristic
3-D structure and catalytic properties. The purified N-terminal
truncated forms of a pancreatic (from ostrich) and a fungal
(from Rhizopus oryzae, ROL32) (sayari et al.,
2005) lipases displayed much lower activities as compared
to the native proteins. The aim of this study is to explain
this common functional feature on a structural basis. The
molecular modelling showed that the N-terminal peptide of
the fungal lipase displays an extended “V” shaped
structure motif (sayari et al., 2005). We observed
that the N-terminal peptide of a pancreatic lipase shares
the same extended structure with that of the ROL32, despite
the low sequence homology between the two peptides. Upon superim-position
of the 3-D structure of the N-terminal catalytic domain of
the pancreatic lipase with the model of the ROL32, we have
shown that the N-terminal peptide and the open lid domain,
of each lipase, are located distally within the putative interfacial
binding surface. In particular, two hydrophobic residues,
Leu and Ile belonging to the N-terminal peptide of each lipase
are well placed to interact with the lipidic substrate. Furthermore,
the N-terminal peptide of each lipase seems to be well placed
to interact with the loop bearing the catalytic aspartic acid.
All these observations might explain the fact that the loss
of the N-terminal peptide affects the lipase activity. This
work shows that the two lipases share striking structural
and functional features with respect to their N-terminal peptide
despite the fact that they belong to very distant kingdoms
such as fungal and higher animals’ ones.
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Copper (II) - HisAibGly Complex and
Its Superoxide Dismutase Activity
R.K. Singh, S. Prasad and U.P. Singh
The superoxide anion radical is a highly reactive toxic
species produced during metabolic processes. Several copper
(II) complexes with peptides are known to show superoxide
dismutase (SOD) activity but those having a peptide with a
non-natural amino acid are limited. The synthesis of HisAibGly
peptide and its complexation with copper (II) ions has been
reported. The interaction of the synthetic peptide with Cu(II)
was studied by electron spray ionization-mass (ESI-MS), circular
dichroism (CD), absorption (UV-Vis) and electron paramagnetic
resonance (EPR) spectroscopic methods. The solution studies
and species distribution were performed by both spectrophotometric
and potentiometric methods. The studies were performed at
25 ±
0.1 °C with constant ionic strength (μ
= 0.1 M NaNO3) in aqueous
solution using Bjerrum-Calvin’s pH-titration technique
as adopted by Irving and Rossotti for binary systems. The
species distribution stidies indicated that the complexation
occurred from 3-11 pH and a three nitrogen coordinated species
predominates at 8-9 whereas a four nitrogen coordinated species
was formed between pH 9-11. The copper-peptide complex was
tested for SOD activity using xanthine-xanthine oxidase -
nitroblue tetrazolium (NBT) methods.
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Toward the Virtual Screening of Potential Drugs
in the Homology Modeled NAD+
Dependent DNA Ligase from Mycobacterium tuberculosis
V. Singh and P. Somvanshi
DNA ligase is an important enzyme and it plays vital role
in the replication and repair; also catalyzes nick joining
between adjacent bases of DNA. The NAD+
dependent DNA ligase is selectively present in eubacteria
and few viruses; but missing in humans. Homology modeling
was used to generate 3-D structure of NAD+
dependent DNA ligase (LigA) of Mycobacterium tuberculosis
using the known template (PDB: 2OWO). Furthermore, the stereochemical
quality and torsion angle of 3-D structure was validated.
Numerous effective drugs were selected and the active amino
acid residue in LigA was targeted and virtual screening through
molecular docking was done. In this analysis, four drugs Chloroquine,
Hydroxychloroquine, Putrienscine and Adriamycin were found
more potent in inhibition of M. tuberculosis through
the robust binding affinity between protein-drug interactions
in comparison with the other studied drugs. A phylogenetic
tree was constructed and it was observed that homology of
LigA in M. tuberculosis resembled with other Mycobacterium
species. The conserved active amino acids of LigA may be useful
to target these drugs. These findings could be used as the
starting point of a rational design of novel antibacterial
drugs and its analogs. |
