TY - JOUR
T1 - Sequence and structure insights of kazal type thrombin inhibitor protein
T2 - Studied with phylogeny, homology modeling and dynamic MM/GBSA studies
AU - Jadhav, Aparna
AU - Dash, Radha Charan
AU - Hirwani, Raj
AU - Abdin, Malik
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/3
Y1 - 2018/3
N2 - Despite the wide medical importance of serine protease inhibitors, many of kazal type proteins are still to be explored. These thrombin inhibiting proteins are found in the digestive system of hematophagous organisms mainly Arthropods. We studied one of such protein i.e. Kazal type-1 protein from sand-fly Phlebotomus papatasi as its structure and interaction with thrombin is unclear. Initially, Dipetalin a kazal-follistasin domain protein was run through PSI-BLAST to retrieve related sequences. Using this set of sequence a phylogenetic tree was constructed, which identified a distantly related kazal type-1 protein. A three-dimensional structure was predicted for this protein and was aligned with Rhodniin for further evaluation. To have a comparative understanding of it's binding at the thrombin active site, the aligned kazal model-thrombin and rhodniin-thrombin complexes were subjected to molecular dynamics simulations. Dynamics analysis with reference to main chain RMSD, H-chain residue RMSF and total energy showed rhodniin-thrombin complex as a more stable system. Further, the MM/GBSA method was applied that calculated the binding free energy (ΔGbinding) for rhodniin and kazal model as −220.32 kcal/Mol and −90.70 kcal/Mol, respectively. Thus, it shows that kazal model has weaker bonding with thrombin, unlike rhodniin.
AB - Despite the wide medical importance of serine protease inhibitors, many of kazal type proteins are still to be explored. These thrombin inhibiting proteins are found in the digestive system of hematophagous organisms mainly Arthropods. We studied one of such protein i.e. Kazal type-1 protein from sand-fly Phlebotomus papatasi as its structure and interaction with thrombin is unclear. Initially, Dipetalin a kazal-follistasin domain protein was run through PSI-BLAST to retrieve related sequences. Using this set of sequence a phylogenetic tree was constructed, which identified a distantly related kazal type-1 protein. A three-dimensional structure was predicted for this protein and was aligned with Rhodniin for further evaluation. To have a comparative understanding of it's binding at the thrombin active site, the aligned kazal model-thrombin and rhodniin-thrombin complexes were subjected to molecular dynamics simulations. Dynamics analysis with reference to main chain RMSD, H-chain residue RMSF and total energy showed rhodniin-thrombin complex as a more stable system. Further, the MM/GBSA method was applied that calculated the binding free energy (ΔGbinding) for rhodniin and kazal model as −220.32 kcal/Mol and −90.70 kcal/Mol, respectively. Thus, it shows that kazal model has weaker bonding with thrombin, unlike rhodniin.
KW - Binding energy
KW - Homology modeling
KW - Kazal protein
KW - MM/GBSA
KW - Molecular dynamics
KW - Phylogeny
UR - http://www.scopus.com/inward/record.url?scp=85033577626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033577626&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2017.11.020
DO - 10.1016/j.ijbiomac.2017.11.020
M3 - Article
C2 - 29129633
AN - SCOPUS:85033577626
SN - 0141-8130
VL - 108
SP - 1045
EP - 1052
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -