TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled  Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling  [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it\u27s docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction. © 2016 The Authors

Chitranshi, Nitin

Dheer, Yogita

Graham, Stuart

Gupta, Veer

Gupta, Vivek

Vander Wall, Roshana

Data in Brief

English

PubMed

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled "Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling" [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it's docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction.7 page(s

Macquarie University ResearchOnline

Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled “Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling” [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it’s docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction. Keywords: TrkB, Cyclotraxin B, GSK3β, Dockin

Nitin Chitranshi

Vivek Gupta

Yogita Dheer

Veer Gupta

Roshana Vander Wall

Stuart Graham

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AbstractTrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled “Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling” [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it’s docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction

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Data in Brief
Data in Brief 6 (2016) 776–782http://d
2352-34
(http://c
n Corr
E-m
1 Thjournal homepage: www.elsevier.com/locate/dibData ArticleMolecular determinants and interaction data
of cyclic peptide inhibitor with the extracellular
domain of TrkB receptor
Nitin Chitranshi a,n,1, Vivek Gupta a,1, Yogita Dheer a,
Veer Gupta b, Roshana Vander Wall a, Stuart Grahama,c
a Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde,
NSW 2109, Australia
b School of Medical Sciences, Edith Cowan University, Perth, Australia
c Save Sight Institute, Sydney University, Sydney, NSW 2109, Australiaa r t i c l e i n f o
Article history:
Received 13 October 2015
Received in revised form
29 December 2015
Accepted 8 January 2016
Available online 16 January 2016
Keywords:
TrkB
Cyclotraxin B
GSK3β
Dockingx.doi.org/10.1016/j.dib.2016.01.016
09/& 2016 The Authors. Published by Else
reativecommons.org/licenses/by/4.0/).
esponding author.
ail addresses: nitinchitranshi@gmail.com (N
ese authors contributed equally to this woa b s t r a c t
TrkB is a high afﬁnity receptor for the brain derived neurotrophic
factor (BDNF) and its phosphorylation stimulates activation of
several intracellular signalling pathways linked to cellular growth,
differentiation and maintenance. Identiﬁcation of various activa-
tors and inhibitors of the TrkB receptor and greater understanding
their binding mechanisms is critical to elucidate the biochemical
and pharmacological pathways and analyse various protein crys-
tallization studies. The data presented here is related to the
research article entitled “Brain Derived neurotrophic factor is
involved in the regulation of glycogen synthase kinase 3β (GSK3β)
signalling” [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked
cyclic peptide molecule that interacts with TrkB receptor and
inhibits the BDNF/TrkB downstream signalling. This article reports
for the ﬁrst time binding mechanism and interaction parameters of
CTXB with the TrkB receptor. The molecular model of CTXB has
been generated and it’s docking with TrkB domain carried out to
determine the critical residues involved in the protein peptide
interaction.
& 2016 The Authors. Published by Elsevier Inc. This is an open
access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).vier Inc. This is an open access article under the CC BY license
. Chitranshi), vivek.gupta@mq.edu.au (V. Gupta).
rk.
N. Chitranshi et al. / Data in Brief 6 (2016) 776–782 777Speciﬁcations TableS
M
T
H
D
E
E
Dubject area Biology
ore speciﬁc subject area Protein-peptide binding and interactions
ype of data Table, protein-peptide interaction images and tables
ow data was acquired Molecular modeling and in silico analysis
ata format Analysed
xperimental factors Molecular modeling and docking
xperimental features Amino acid orientations and type of interactions, energy minimization.
ata source location Australia
ata accessibility Data within this articleD
Value of the data
 Three dimensional molecular model of the cyclic peptide cyclotraxin B was generated for the ﬁrst
time to determine its interactions with the TrkB receptor.
 Future studies to determine pharmacological, biochemical or interaction studies of TrkB receptor or
related molecules will be facilitated by the interaction and binding parameters reported here.
 Binding interactions of CTXB with TrkB will determine its potential usage in pharmacological
studies and development of new derivatives and ligands.1. Data
The data shown here elucidates molecular modeling of cyclic peptide cyclotraxin B which is a TrkB
inhibitor. Active site of the extracellular D5 domain of the TrkB receptor which is primarily involved in
this interaction was also modelled. Finally the cyclic peptide inhibitor was also identiﬁed and docking
carried out with the extracellular D5 domain of TrkB. The interacting amino acid residues that are
involved in docking are identiﬁed and various interaction parameters provided in detail using a
combination of molecular modeling and molecular docking computational tools.2. Experimental design, materials and methods
2.1. Selection and preparation of cyclotraxin B, TrkB inhibitor
Cyclotraxin B (CTXB) is a cyclic peptide chain of 10 amino acid linked by a disulphide bridge [2]. It
is an inhibitor of the TrkB receptor activation and its downstream signalling pathway mediated by
BDNF binding [1,3–5]. Cyclization is important to provide stability to the peptide macromolecule. The
primary structure of the peptide is known and in this manuscript we report for the ﬁrst time the
putative three dimensional structure of the peptide (Fig. 1A). The two dimensional (2D) and three
dimensional (3D) structure of the CTXB was built using ChemDraw Ultra 8.0 (Cambridgesoft, Wal-
tham, MA, USA) (Fig. 1B and C). Extensive energy minimization was performed using the Austin
Model-1 (AM1) programme until the root mean square (RMS) gradient value became smaller than 0.
100 kcal/mol Å. The molecule was further subjected to re-optimization via MOPAC (Molecular Orbital
Package) method [6] until the RMS gradient attained a value lesser than 0.0001 kcal/mol Å. The
chemical properties of CTXB was calculated by ACD (Advanced Chemistry Development, Canada) labs
Chemsketch software and the data is presented in Table 1 [7].
2.2. Molecular modeling and generation of TrkB binding region
The primary structure of TrkB receptor and its various domains were examined [8]. Crystal
structure of the extracellular D5 domain of the TrkB which exhibits binding with the human
Table 1
The chemical property and the calculation of cyclotraxin B (CTXB) as evaluated using ACD labs Chemsketch software.
Chemical properties Calculations
Molecular formula C48H73N13O17S3
Formula weight 1200.36512
Composition C(48.03%) H(6.13%) N(15.17%) O(22.66%) S(8.01%)
Molar refractivity 296.2570.4 cm3
Molar volume 805.875.0 cm3
Parachor 2467.976.0 cm3
Index of refraction 1.65670.03
Surface tension 87.975.0 dyne/cm
Density 1.4870.1 g/cm3
Dielectric constant Not available
Polarizability 117.4470.5 10-24 cm3
Monoisotopic mass 1199.440948 Da
Nominal mass 1199 Da
Average mass 1200.3651 Da
Fig. 1. Cyclotraxin B stuructre (A) one dimensional, (B) two dimensional and (C) three dimensional view.
N. Chitranshi et al. / Data in Brief 6 (2016) 776–782778Neurotrophin-4/5 (NT-4/5) ligand (PDB id: 1HCF) was selected from the protein databank [9]. The
asymmetric unit of the crystal structure contains a single copy of the TrkB-D5:NT-4/5 complex,
comprising one homodimer of NT-4/5 bound to two monomers of TrkB-D5. The two monomer chain
of TrkB-D5 (chains X and Y) are identical. These chains are known to interact with the BDNF/ NT-4/5
protein. Only chain X of PDB id 1HCF was considered in the present study for its potential interactions
with the CTXB that highlights the location of the conserved interaction site. The optimization of
proteins was carried out using well characterized UCSF Chimera software (San Francisco, California,
USA), implying amber parameters, followed by minimization with MMTK (Molecular Modeling
Toolkit) method. The steepest minimizations was ﬁrst performed in 1000 steps to relieve highly
unfavourable clashes than followed by conjugate gradient minimization in 500 steps with a step size
of 0.02 Å for more effective reaching an energy minimum [10, 11].
Fig. 2. Predicted binding sites of CTXB peptide ‘‘CNPMGYTKEG’’ core motif on the surface of TrkB-D5 domain as predicted by
the PEPSITE2 programme. The six ball shaped structures indicate the predicted locations of six residues from ‘‘CNPMGYTKEG’’.
(1–8) distribution of 6 amino acids of the peptide predicted on the surface of TrkB-D5 in the sequence of Cys (C), Asn (N), Pro
(P), Met (M), Tyr (Y) and Lys (K) (labelled) and (9–10) distribution of 6 selected amino acids of CTXB binding to TrkB-D5-Pro (P),
Met (M), Gly (G), Tyr (Y), Thr (T) and Lys (K) (labelled).
Table 2
PepSite2 binding score prediction of selected cyclotraxin B (CTXB) residue sequences to the TrkB-
D5 domain.
Rank Peptide sequence order Pepsite2 score
1 CNPMYK 0.02733
2 CNPMYK 0.03015
3 CNPMYK 0.03266
4 CNPMYK 0.03583
5 CNPMYK 0.03719
6 CNPMYK 0.04098
7 CNPMYK 0.04435
8 CNPMYK 0.04993
9 PMGYTK 0.05985
10 PMGYTK 0.06992
N. Chitranshi et al. / Data in Brief 6 (2016) 776–782 7792.3. Identiﬁcation of CTXB binding site
The protein motif was subjected to in silico assessment of the potential binding of selected CTXB
residues to different regions on the TrkB D5 surfaces. This binding interactions were assessed in terms
of probability of CTXB participating residues binding to the TrkB D5 receptor surface and theoretical
scores determined using the PepSite2 server [12]. Peptide binding may also affect the tyrosine
phosphorylation proﬁle [13] of the TrkB receptor translating into its altered activity which can be
assessed in future investigations. Surface accessibility of the ligand to various binding pockets was
also examined [14].
PepSite2 is a computational tool that scans the surface of a given protein for patches or grooves
that are likely to inﬂuence binding of individual amino acid residues or peptides up to ten amino acids
and provides a score that reﬂects the propensity of the peptide to bind to that region. The PepSite
score is expressed in relative units and the higher scores reﬂects superior binding. We applied PepSite
in a sliding window of 10 residues to assess the binding of the TrkB-D5 domain and CTXB peptide
sequence (CNPMGYTKEG). The scores of the CTXB binding to different regions of TrkB D5 domain are
presented (Fig. 2A, Model 1, Table 2) [1].
Table 3
The top 20 docking scores and geometrical parameters of the peptide CTXB with TrkB-D5 domain; ACE: Atomic Contact Energy.
Rank Score Area ACE Transformation
1 5538 652.1 344.82 0.57 1.01 2.62 10.48 3.78 29.57
2 5282 597.6 272.85 1.01 0.26 0.32 12.66 4.68 28.84
3 5100 620 330.86 –1.52 0.07 0.81 –11.83 –7.13 27.44
4 4966 528.9 126.23 –0.31 –0.63 –2.16 –22.34 8.83 21.59
5 4878 623.4 300.47 2.71 0.78 1.27 13.25 4.12 29.20
6 4824 571.7 214.66 –0.11 1.20 2.50 –5.75 11.23 7.03
7 4800 621.7 217.57 –2.59 –0.46 0.54 –22.14 6.07 23.60
8 4678 531.9 182.76 0.67 0.16 1.87 20.33 9.72 23.42
9 4654 512.8 234.35 0.84 0.57 0.51 12.13 2.05 31.89
10 4642 570.9 250.43 1.34 0.11 1.76 23.69 10.32 20.31
11 4606 539.9 170.59 0.32 1.01 2.51 22.65 10.28 21.86
12 4536 521.6 189.48 3.07 0.42 0.56 20.13 9.32 24.74
13 4530 735.8 436.61 0.46 1.21 2.78 3.58 11.15 12.99
14 4522 622 273.37 1.99 0.45 2.81 8.24 1.98 30.78
15 4358 547.6 276.07 0.05 0.96 2.97 7.11 6.08 31.48
16 4264 468.6 196.84 2.26 –0.23 2.23 –1.86 14.82 14.52
17 4242 531.7 154.98 0.67 –0.38 2.13 16.81 14.23 21.56
18 4240 548.7 304.69 0.50 0.35 0.24 6.28 11.67 5.72
19 4234 458.8 155.03 2.26 0.60 2.85 2.98 13.89 13.16
20 4230 653.7 351.22 0.76 1.23 2.83 5.51 13.82 10.66
Fig. 3. Interacting residues and binding mode of CTXB with TrkB-D5 domain (A) Docking of TrkB (ribbon structure) with the
CTXB (stick model) showing critical residues (rank 1) involved in interaction, (B) enlarged view of the interaction pocket within
5.5 Å region around the ligand, CTXB-TrkB-D5 complex and (C) surface view showing the grove in TrkB-D5 domain (Cyan)
locating CTXB peptide (pink). Green dashed line denotes the hydrogen bonding and brown dashed line reﬂects pi-sulpha
interactions and stacking. The images were generated with the Discovery Studio 4.0 Client (Accelrys, Inc., San Diego, CA, USA).
N. Chitranshi et al. / Data in Brief 6 (2016) 776–782780
N. Chitranshi et al. / Data in Brief 6 (2016) 776–782 7812.4. Peptide docking in the binding region
The protein-peptide docking was performed with the PatchDock software available in the public
domain [15]. The crystal structure of TrkB (PDB ID: 1HCF) was retrieved from Protein Data Bank. The
single chain of TrkB-D5 as described previously was used for docking study under default complex-
type settings. Molecular visualization and general analysis were done using the program PyMOL and
Discovery Studio 4.0 softwares [16]. TrkB residues closer than 5.5 Å to any of the C-terminal NT-4/5
amino acids (Cys345-Asn350) were selected for docking (Fig. S1). The docking scores, atomic contact
energies and geometrical parameters are compiled as Table 3. The hydrogen bond between TrkB-D5
and CTXB (rank 1) was observed to be formed between the amino acid residues His353, Met354,
Ala376, His377 and Trp381 (Fig. 3A). The pi-sulpha interaction was also observed between CTXB and
Met354 (Fig. 3B). Surface binding of CTXB with TrkB-D5 domain is shown in Fig. 3C. The selected
binding pocket of TrkB-D5 was observed to overlap with the C-terminal region of the NT-4/5 binding
site (Fig. S2). The two dimensional (2D) interaction map was created by LigPlotþ which helped to
identify new interacting residues in the TrKB-D5:CTXB complex [17]. Ser294, Asn320, Gln373 and
Ser375 of TrkB-D5 were identiﬁed to form hydrogen bonds with CTXB. Trp381 was observed to be
involved in CTXB TrkBD5 binding using both the Discovery Studio 4.0 as well as the LigPlotþ pro-
grammes (Fig. S3).Acknowledgements
Supported by funds from the NHMRC, Ophthalmic Research Institute of Australia (ORIA) and
MQRDG (9201301278) grants.Appendix A. Supplementary material
Supplementary data associated with this article can be found in the online version at http://dx.doi.
org/10.1016/j.dib.2016.01.016.References
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Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor 

Research Online @ ECU

Edith Cowan University Research Online ECU Publications Post 2013 2016 Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor Nitin Chitranshi Vivek Gupta Yogita Dheer Veer Gupta Edith Cowan University, v.gupta@ecu.edu.au Roshana Vander Wall See next page for additional authors Follow this and additional works at: https://ro.ecu.edu.au/ecuworkspost2013  Part of the Chemical and Pharmacologic Phenomena Commons, and the Medical Pharmacology Commons 10.1016/j.dib.2016.01.016 Chitranshi, N., Gupta, V., Dheer, Y., Gupta, V., Vander Wall, R., & Graham, S. (2016). Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor. Data in Brief, 6, 776-782. Available here. This Journal Article is posted at Research Online. https://ro.ecu.edu.au/ecuworkspost2013/1532 Authors Nitin Chitranshi, Vivek Gupta, Yogita Dheer, Veer Gupta, Roshana Vander Wall, and Stuart Graham This journal article is available at Research Online: https://ro.ecu.edu.au/ecuworkspost2013/1532 Data ArticleMolecular determinants and interaction dataof cyclic peptide inhibitor with the extracellulardomain of TrkB receptorNitin Chitranshi a,n,1, Vivek Gupta a,1, Yogita Dheer a,Veer Gupta b, Roshana Vander Wall a, Stuart Grahama,ca Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde,NSW 2109, Australiab School of Medical Sciences, Edith Cowan University, Perth, Australiac Save Sight Institute, Sydney University, Sydney, NSW 2109, Australiaa r t i c l e i n f oArticle history:Received 13 October 2015Received in revised form29 December 2015Accepted 8 January 2016Available online 16 January 2016Keywords:TrkBCyclotraxin BGSK3βDockinga b s t r a c tTrkB is a high affinity receptor for the brain derived neurotrophicfactor (BDNF) and its phosphorylation stimulates activation ofseveral intracellular signalling pathways linked to cellular growth,differentiation and maintenance. Identification of various activa-tors and inhibitors of the TrkB receptor and greater understandingtheir binding mechanisms is critical to elucidate the biochemicaland pharmacological pathways and analyse various protein crys-tallization studies. The data presented here is related to theresearch article entitled “Brain Derived neurotrophic factor isinvolved in the regulation of glycogen synthase kinase 3β (GSK3β)signalling” [1]. Cyclotraxin B (CTXB) is a disulphide bridge linkedcyclic peptide molecule that interacts with TrkB receptor andinhibits the BDNF/TrkB downstream signalling. This article reportsfor the first time binding mechanism and interaction parameters ofCTXB with the TrkB receptor. The molecular model of CTXB hasbeen generated and it’s docking with TrkB domain carried out todetermine the critical residues involved in the protein peptideinteraction.& 2016 The Authors. Published by Elsevier Inc. This is an openaccess article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).Contents lists available at ScienceDirectjournal homepage: www.elsevier.com/locate/dibData in Briefhttp://dx.doi.org/10.1016/j.dib.2016.01.0162352-3409/& 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).n Corresponding author.E-mail addresses: nitinchitranshi@gmail.com (N. Chitranshi), vivek.gupta@mq.edu.au (V. Gupta).1 These authors contributed equally to this work.Data in Brief 6 (2016) 776–782Specifications TableSubject area BiologyMore specific subject area Protein-peptide binding and interactionsType of data Table, protein-peptide interaction images and tablesHow data was acquired Molecular modeling and in silico analysisData format AnalysedExperimental factors Molecular modeling and dockingExperimental features Amino acid orientations and type of interactions, energy minimization.Data source location AustraliaData accessibility Data within this articleValue of the data Three dimensional molecular model of the cyclic peptide cyclotraxin B was generated for the firsttime to determine its interactions with the TrkB receptor. Future studies to determine pharmacological, biochemical or interaction studies of TrkB receptor orrelated molecules will be facilitated by the interaction and binding parameters reported here. Binding interactions of CTXB with TrkB will determine its potential usage in pharmacologicalstudies and development of new derivatives and ligands.1. DataThe data shown here elucidates molecular modeling of cyclic peptide cyclotraxin B which is a TrkBinhibitor. Active site of the extracellular D5 domain of the TrkB receptor which is primarily involved inthis interaction was also modelled. Finally the cyclic peptide inhibitor was also identified and dockingcarried out with the extracellular D5 domain of TrkB. The interacting amino acid residues that areinvolved in docking are identified and various interaction parameters provided in detail using acombination of molecular modeling and molecular docking computational tools.2. Experimental design, materials and methods2.1. Selection and preparation of cyclotraxin B, TrkB inhibitorCyclotraxin B (CTXB) is a cyclic peptide chain of 10 amino acid linked by a disulphide bridge [2]. Itis an inhibitor of the TrkB receptor activation and its downstream signalling pathway mediated byBDNF binding [1,3–5]. Cyclization is important to provide stability to the peptide macromolecule. Theprimary structure of the peptide is known and in this manuscript we report for the first time theputative three dimensional structure of the peptide (Fig. 1A). The two dimensional (2D) and threedimensional (3D) structure of the CTXB was built using ChemDraw Ultra 8.0 (Cambridgesoft, Wal-tham, MA, USA) (Fig. 1B and C). Extensive energy minimization was performed using the AustinModel-1 (AM1) programme until the root mean square (RMS) gradient value became smaller than 0.100 kcal/mol Å. The molecule was further subjected to re-optimization via MOPAC (Molecular OrbitalPackage) method [6] until the RMS gradient attained a value lesser than 0.0001 kcal/mol Å. Thechemical properties of CTXB was calculated by ACD (Advanced Chemistry Development, Canada) labsChemsketch software and the data is presented in Table 1 [7].2.2. Molecular modeling and generation of TrkB binding regionThe primary structure of TrkB receptor and its various domains were examined [8]. Crystalstructure of the extracellular D5 domain of the TrkB which exhibits binding with the humanN. Chitranshi et al. / Data in Brief 6 (2016) 776–782 777Neurotrophin-4/5 (NT-4/5) ligand (PDB id: 1HCF) was selected from the protein databank [9]. Theasymmetric unit of the crystal structure contains a single copy of the TrkB-D5:NT-4/5 complex,comprising one homodimer of NT-4/5 bound to two monomers of TrkB-D5. The two monomer chainof TrkB-D5 (chains X and Y) are identical. These chains are known to interact with the BDNF/ NT-4/5protein. Only chain X of PDB id 1HCF was considered in the present study for its potential interactionswith the CTXB that highlights the location of the conserved interaction site. The optimization ofproteins was carried out using well characterized UCSF Chimera software (San Francisco, California,USA), implying amber parameters, followed by minimization with MMTK (Molecular ModelingToolkit) method. The steepest minimizations was first performed in 1000 steps to relieve highlyunfavourable clashes than followed by conjugate gradient minimization in 500 steps with a step sizeof 0.02 Å for more effective reaching an energy minimum [10, 11].Table 1The chemical property and the calculation of cyclotraxin B (CTXB) as evaluated using ACD labs Chemsketch software.Chemical properties CalculationsMolecular formula C48H73N13O17S3Formula weight 1200.36512Composition C(48.03%) H(6.13%) N(15.17%) O(22.66%) S(8.01%)Molar refractivity 296.2570.4 cm3Molar volume 805.875.0 cm3Parachor 2467.976.0 cm3Index of refraction 1.65670.03Surface tension 87.975.0 dyne/cmDensity 1.4870.1 g/cm3Dielectric constant Not availablePolarizability 117.4470.5 10-24 cm3Monoisotopic mass 1199.440948 DaNominal mass 1199 DaAverage mass 1200.3651 DaFig. 1. Cyclotraxin B stuructre (A) one dimensional, (B) two dimensional and (C) three dimensional view.N. Chitranshi et al. / Data in Brief 6 (2016) 776–7827782.3. Identification of CTXB binding siteThe protein motif was subjected to in silico assessment of the potential binding of selected CTXBresidues to different regions on the TrkB D5 surfaces. This binding interactions were assessed in termsof probability of CTXB participating residues binding to the TrkB D5 receptor surface and theoreticalscores determined using the PepSite2 server [12]. Peptide binding may also affect the tyrosinephosphorylation profile [13] of the TrkB receptor translating into its altered activity which can beassessed in future investigations. Surface accessibility of the ligand to various binding pockets wasalso examined [14].PepSite2 is a computational tool that scans the surface of a given protein for patches or groovesthat are likely to influence binding of individual amino acid residues or peptides up to ten amino acidsand provides a score that reflects the propensity of the peptide to bind to that region. The PepSitescore is expressed in relative units and the higher scores reflects superior binding. We applied PepSitein a sliding window of 10 residues to assess the binding of the TrkB-D5 domain and CTXB peptidesequence (CNPMGYTKEG). The scores of the CTXB binding to different regions of TrkB D5 domain arepresented (Fig. 2A, Model 1, Table 2) [1].Fig. 2. Predicted binding sites of CTXB peptide ‘‘CNPMGYTKEG’’ core motif on the surface of TrkB-D5 domain as predicted bythe PEPSITE2 programme. The six ball shaped structures indicate the predicted locations of six residues from ‘‘CNPMGYTKEG’’.(1–8) distribution of 6 amino acids of the peptide predicted on the surface of TrkB-D5 in the sequence of Cys (C), Asn (N), Pro(P), Met (M), Tyr (Y) and Lys (K) (labelled) and (9–10) distribution of 6 selected amino acids of CTXB binding to TrkB-D5-Pro (P),Met (M), Gly (G), Tyr (Y), Thr (T) and Lys (K) (labelled).Table 2PepSite2 binding score prediction of selected cyclotraxin B (CTXB) residue sequences to the TrkB-D5 domain.Rank Peptide sequence order Pepsite2 score1 CNPMYK 0.027332 CNPMYK 0.030153 CNPMYK 0.032664 CNPMYK 0.035835 CNPMYK 0.037196 CNPMYK 0.040987 CNPMYK 0.044358 CNPMYK 0.049939 PMGYTK 0.0598510 PMGYTK 0.06992N. Chitranshi et al. / Data in Brief 6 (2016) 776–782 779Table 3The top 20 docking scores and geometrical parameters of the peptide CTXB with TrkB-D5 domain; ACE: Atomic Contact Energy.Rank Score Area ACE Transformation1 5538 652.1 344.82 0.57 1.01 2.62 10.48 3.78 29.572 5282 597.6 272.85 1.01 0.26 0.32 12.66 4.68 28.843 5100 620 330.86 –1.52 0.07 0.81 –11.83 –7.13 27.444 4966 528.9 126.23 –0.31 –0.63 –2.16 –22.34 8.83 21.595 4878 623.4 300.47 2.71 0.78 1.27 13.25 4.12 29.206 4824 571.7 214.66 –0.11 1.20 2.50 –5.75 11.23 7.037 4800 621.7 217.57 –2.59 –0.46 0.54 –22.14 6.07 23.608 4678 531.9 182.76 0.67 0.16 1.87 20.33 9.72 23.429 4654 512.8 234.35 0.84 0.57 0.51 12.13 2.05 31.8910 4642 570.9 250.43 1.34 0.11 1.76 23.69 10.32 20.3111 4606 539.9 170.59 0.32 1.01 2.51 22.65 10.28 21.8612 4536 521.6 189.48 3.07 0.42 0.56 20.13 9.32 24.7413 4530 735.8 436.61 0.46 1.21 2.78 3.58 11.15 12.9914 4522 622 273.37 1.99 0.45 2.81 8.24 1.98 30.7815 4358 547.6 276.07 0.05 0.96 2.97 7.11 6.08 31.4816 4264 468.6 196.84 2.26 –0.23 2.23 –1.86 14.82 14.5217 4242 531.7 154.98 0.67 –0.38 2.13 16.81 14.23 21.5618 4240 548.7 304.69 0.50 0.35 0.24 6.28 11.67 5.7219 4234 458.8 155.03 2.26 0.60 2.85 2.98 13.89 13.1620 4230 653.7 351.22 0.76 1.23 2.83 5.51 13.82 10.66Fig. 3. Interacting residues and binding mode of CTXB with TrkB-D5 domain (A) Docking of TrkB (ribbon structure) with theCTXB (stick model) showing critical residues (rank 1) involved in interaction, (B) enlarged view of the interaction pocket within5.5 Å region around the ligand, CTXB-TrkB-D5 complex and (C) surface view showing the grove in TrkB-D5 domain (Cyan)locating CTXB peptide (pink). Green dashed line denotes the hydrogen bonding and brown dashed line reflects pi-sulphainteractions and stacking. The images were generated with the Discovery Studio 4.0 Client (Accelrys, Inc., San Diego, CA, USA).N. Chitranshi et al. / Data in Brief 6 (2016) 776–7827802.4. Peptide docking in the binding regionThe protein-peptide docking was performed with the PatchDock software available in the publicdomain [15]. The crystal structure of TrkB (PDB ID: 1HCF) was retrieved from Protein Data Bank. Thesingle chain of TrkB-D5 as described previously was used for docking study under default complex-type settings. Molecular visualization and general analysis were done using the program PyMOL andDiscovery Studio 4.0 softwares [16]. TrkB residues closer than 5.5 Å to any of the C-terminal NT-4/5amino acids (Cys345-Asn350) were selected for docking (Fig. S1). The docking scores, atomic contactenergies and geometrical parameters are compiled as Table 3. The hydrogen bond between TrkB-D5and CTXB (rank 1) was observed to be formed between the amino acid residues His353, Met354,Ala376, His377 and Trp381 (Fig. 3A). The pi-sulpha interaction was also observed between CTXB andMet354 (Fig. 3B). Surface binding of CTXB with TrkB-D5 domain is shown in Fig. 3C. The selectedbinding pocket of TrkB-D5 was observed to overlap with the C-terminal region of the NT-4/5 bindingsite (Fig. S2). The two dimensional (2D) interaction map was created by LigPlotþ which helped toidentify new interacting residues in the TrKB-D5:CTXB complex [17]. Ser294, Asn320, Gln373 andSer375 of TrkB-D5 were identified to form hydrogen bonds with CTXB. Trp381 was observed to beinvolved in CTXB TrkBD5 binding using both the Discovery Studio 4.0 as well as the LigPlotþ pro-grammes (Fig. S3).AcknowledgementsSupported by funds from the NHMRC, Ophthalmic Research Institute of Australia (ORIA) andMQRDG (9201301278) grants.Appendix A. Supplementary materialSupplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.dib.2016.01.016.References[1] V. Gupta, N. Chitranshi, Y. You, A. Klistorner, S. Graham, Brain derived neurotrophic factor is involved in the regulation ofglycogen synthase kinase 3beta (GSK3beta) signalling, Biochem. Biophys. Res. Commun. 454 (2014) 381–386.[2] V.K. Gupta, Y. You, J.C. Li, A. Klistorner, S.L. 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Seth, New molecular scaffolds for the design of Alzheimer's acetylcholinesteraseinhibitors identified using ligand- and receptor-based virtual screening, Med. Chem. Res. 22 (2013) 2328–2345.[12] E. Petsalaki, A. Stark, E. Garcia-Urdiales, R.B. Russell, Accurate prediction of peptide binding sites on protein surfaces, Plos.Comput. Biol. 5 (2009) e1000335.N. Chitranshi et al. / Data in Brief 6 (2016) 776–782 781[13] V.K. Gupta, A. Rajala, R.V. Rajala, Insulin receptor regulates photoreceptor CNG channel activity, Am. J. Physiol. Endocrinol.Metab. 303 (2012) E1363–E1372.[14] V.K. Gupta, L.R. Gowda, Alpha-1-proteinase inhibitor is a heparin binding serpin: molecular interactions with the Lys richcluster of helix-F domain, Biochimie 90 (2008) 749–761.[15] D. Schneidman-Duhovny, Y. Inbar, R. Nussinov, H.J. Wolfson, PatchDock and Symm Dock: servers for rigid and symmetricdocking, Nucleic Acids Res. 33 (2005) W363–W367.[16] A.D. Simmons, T.K. Nguyen, J.L. Follis, A. Ribes-Zamora, Using a PyMOL activity to reinforce the connection betweengenotype and phenotype in an undergraduate genetics laboratory, Plos. One 9 (2014) e114257.[17] R.A. Laskowski, M.B. Swindells, LigPlotþ: multiple ligand-protein interaction diagrams for drug discovery, J. Chem. Inf.Model. 51 (2011) 2778–2786.N. Chitranshi et al. / Data in Brief 6 (2016) 776–782782

Chitranshi, N

Gupta, V

Dheer, Y

Vander Wall, R

Graham, S

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Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor

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