Understanding Russell’s viper venom factor V activator’s substrate specificity by surface plasmon resonance and in-silico studies.
| Title: | Understanding Russell’s viper venom factor V activator’s substrate specificity by surface plasmon resonance and in-silico studies. |
|---|---|
| Authors: | Yadav, Pradeep K.1, Antonyraj, Christian B.1, Basheer Ahamed, Syed Ibrahim1 ibrahim.bic@pondiuni.edu.in, Srinivas, Sistla2 |
| Source: | PLoS ONE. 7/21/2017, Vol. 12 Issue 7, p1-22. 22p. |
| Subject Terms: | *SNAKE venom, *RUSSELL'S viper, *BLOOD coagulation factor V, *BIOCHEMICAL substrates, *SURFACE plasmon resonance, *PROTEINASES |
| Abstract: | Blood coagulation factor V (FV) is activated either by Factor X or thrombin, cleaving at three different sites viz., Site I (Arg709-Ser710), site II (Arg1018-Thr1019), and site III (Arg1545-Ser1546). Russell’s viper venom factor V activator (RVV-V) is a thrombin-like serine proteinase that activates FV with selective, single cleavage at site III. A long lasting effort is being pending in understanding the ‘selective’ binding specificity of the RVV-V towards site III. Here, we present the binding kinetic study of RVV-V with two designed peptides corresponding to the regions from site I (Gln699—Asn713) and site II (1008Lys—Pro1022), respectively, that include 15 amino acids. Our investigation for justifying the binding efficacy and kinetics of peptides includes SPR method, protein-peptide docking, molecular dynamics simulation, and principal component analysis (PCA). Surprisingly, the SPR experiment disclosed that the Peptide II showed a lower binding affinity with KD of 2.775 mM while the Peptide I showed none. Docking and simulation of both the peptides with RVV-V engaged either rooted or shallow binding for Peptide II and Peptide I respectively. The peptide binding resulted in global conformational changes in the native fold of RVV-V, whereas the similar studies for thrombin failed to make major changes in the native fold. In support, the PCA analysis for RVV-V showed the dislocation of catalytic triad upon binding both the peptides. Hence, RVV-V, a serine protease, is incompetent in cleaving these two sites. This study suggests a transition in RVV-V from the native rigid to the distorted flexible structure and paves a way to design a new peptide substrate/inhibitor. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Understanding Russell’s viper venom factor V activator’s substrate specificity by surface plasmon resonance and in-silico studies. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yadav%2C+Pradeep+K%2E%22">Yadav, Pradeep K.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Antonyraj%2C+Christian+B%2E%22">Antonyraj, Christian B.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Basheer+Ahamed%2C+Syed+Ibrahim%22">Basheer Ahamed, Syed Ibrahim</searchLink><relatesTo>1</relatesTo><i> ibrahim.bic@pondiuni.edu.in</i><br /><searchLink fieldCode="AR" term="%22Srinivas%2C+Sistla%22">Srinivas, Sistla</searchLink><relatesTo>2</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22PLoS+ONE%22">PLoS ONE</searchLink>. 7/21/2017, Vol. 12 Issue 7, p1-22. 22p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22SNAKE+venom%22">SNAKE venom</searchLink><br />*<searchLink fieldCode="DE" term="%22RUSSELL'S+viper%22">RUSSELL'S viper</searchLink><br />*<searchLink fieldCode="DE" term="%22BLOOD+coagulation+factor+V%22">BLOOD coagulation factor V</searchLink><br />*<searchLink fieldCode="DE" term="%22BIOCHEMICAL+substrates%22">BIOCHEMICAL substrates</searchLink><br />*<searchLink fieldCode="DE" term="%22SURFACE+plasmon+resonance%22">SURFACE plasmon resonance</searchLink><br />*<searchLink fieldCode="DE" term="%22PROTEINASES%22">PROTEINASES</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Blood coagulation factor V (FV) is activated either by Factor X or thrombin, cleaving at three different sites viz., Site I (Arg709-Ser710), site II (Arg1018-Thr1019), and site III (Arg1545-Ser1546). Russell’s viper venom factor V activator (RVV-V) is a thrombin-like serine proteinase that activates FV with selective, single cleavage at site III. A long lasting effort is being pending in understanding the ‘selective’ binding specificity of the RVV-V towards site III. Here, we present the binding kinetic study of RVV-V with two designed peptides corresponding to the regions from site I (Gln699—Asn713) and site II (1008Lys—Pro1022), respectively, that include 15 amino acids. Our investigation for justifying the binding efficacy and kinetics of peptides includes SPR method, protein-peptide docking, molecular dynamics simulation, and principal component analysis (PCA). Surprisingly, the SPR experiment disclosed that the Peptide II showed a lower binding affinity with KD of 2.775 mM while the Peptide I showed none. Docking and simulation of both the peptides with RVV-V engaged either rooted or shallow binding for Peptide II and Peptide I respectively. The peptide binding resulted in global conformational changes in the native fold of RVV-V, whereas the similar studies for thrombin failed to make major changes in the native fold. In support, the PCA analysis for RVV-V showed the dislocation of catalytic triad upon binding both the peptides. Hence, RVV-V, a serine protease, is incompetent in cleaving these two sites. This study suggests a transition in RVV-V from the native rigid to the distorted flexible structure and paves a way to design a new peptide substrate/inhibitor. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1371/journal.pone.0181216 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 22 StartPage: 1 Subjects: – SubjectFull: SNAKE venom Type: general – SubjectFull: RUSSELL'S viper Type: general – SubjectFull: BLOOD coagulation factor V Type: general – SubjectFull: BIOCHEMICAL substrates Type: general – SubjectFull: SURFACE plasmon resonance Type: general – SubjectFull: PROTEINASES Type: general Titles: – TitleFull: Understanding Russell’s viper venom factor V activator’s substrate specificity by surface plasmon resonance and in-silico studies. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yadav, Pradeep K. – PersonEntity: Name: NameFull: Antonyraj, Christian B. – PersonEntity: Name: NameFull: Basheer Ahamed, Syed Ibrahim – PersonEntity: Name: NameFull: Srinivas, Sistla IsPartOfRelationships: – BibEntity: Dates: – D: 21 M: 07 Text: 7/21/2017 Type: published Y: 2017 Identifiers: – Type: issn-print Value: 19326203 Numbering: – Type: volume Value: 12 – Type: issue Value: 7 Titles: – TitleFull: PLoS ONE Type: main |
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