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In silico analyses of predicted substitutions in fibrinolytic protein 'Lumbrokinase-6' suggest enhanced activity.

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Title: In silico analyses of predicted substitutions in fibrinolytic protein 'Lumbrokinase-6' suggest enhanced activity.
Authors: Munawar, Sadam1 (AUTHOR), Sagir, Muhammad2 (AUTHOR), Mustafa, Ghulam1 (AUTHOR), Ali, Muhammad Amjad3 (AUTHOR), Niazi, Adnan Khan1 (AUTHOR), Parvaiz, Aqsa1 (AUTHOR), Yasmin, Farkhanda4 (AUTHOR), Mansoor, Farukh5 (AUTHOR), Kanwal, Shamsa5 (AUTHOR), Rasheed, Majeeda6 (AUTHOR), Kehfulvara, Hafiza1 (AUTHOR), Ali, Habib1,7,8 (AUTHOR) habib_ali1417@yahoo.com, Ullah, Sami9 (AUTHOR), Al-Sehemi, Abdullah G.9 (AUTHOR), Khan, Muhammad Sarwar1 (AUTHOR), Joyia, Faiz Ahmad1 (AUTHOR) faizahmad1980@gmail.com
Source: Process Biochemistry. Nov2021, Vol. 110, p292-301. 10p.
Subjects: Recombinant proteins, Plasminogen, Mutant proteins, Glutamic acid, Plasminogen activators, Serine proteinases
Abstract: [Display omitted] • Lumbrokinases are group of serine proteases. • Serine found at position 214 in lumbrokinase improved the activity of lumbrokinase. • In silico tools were used for characterization of mutant Lk-6 proteins. • Serine-Valin214 substitution were direct activation of breaking Arg561-Val562 bond. • The results of this study are step forward towards engineering smart lumbrokinases. Lumbrokinases (LKs) belong to the group serine proteases capable to prevent thrombosis through the proteolysis of both plasminogen-bound and plasminogen-free fibrin molecules. The article presents improved activity of Lumbrokinase-6 (Lk-6) by suggesting the substitution of a Serine found at position 214 (Lk-6) with three other amino acids namely Glutamic acid, Proline and Valine. To characterize the stability, enzyme-substrate interaction and improved activity of three mutant Lk-6 proteins (Lk-Glu214, Lk-Pro214, Lk-Val214) In Silico tools were utilized. Subsequently, Lk-6 wild type and three mutant proteins were subjected to structure prediction, molecular modeling, phylogeny, molecular docking and Protein-Protein Interaction (PPI) using the In Silico tools. Collection and analysis of results revealed that substituted mutation at Ser214 with Valine214 can appreciably stabilize the overall structure of Lk-6 protein and makes its interaction with plasminogen activator physically powerful for higher plasmin activation. Similarly, Serine214 to Valine214 substitution resulted the direct activation of plasmin breakage at the Arg561-Val562 bond. The Arg-Val at position 561–562 in plasminogen and its connection at catalytic site have significantly shown that the predicted residue Valine214 could be further examined through genetic engineering of Lk-6 protein. Therefore, such results are potential steps towards the engineering of smart and active Lks. [ABSTRACT FROM AUTHOR]
Copyright of Process Biochemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 153680769
AccessLevel: 6
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  Label: Title
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  Data: In silico analyses of predicted substitutions in fibrinolytic protein 'Lumbrokinase-6' suggest enhanced activity.
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  Data: <searchLink fieldCode="AR" term="%22Munawar%2C+Sadam%22">Munawar, Sadam</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sagir%2C+Muhammad%22">Sagir, Muhammad</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mustafa%2C+Ghulam%22">Mustafa, Ghulam</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ali%2C+Muhammad+Amjad%22">Ali, Muhammad Amjad</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Niazi%2C+Adnan+Khan%22">Niazi, Adnan Khan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Parvaiz%2C+Aqsa%22">Parvaiz, Aqsa</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yasmin%2C+Farkhanda%22">Yasmin, Farkhanda</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mansoor%2C+Farukh%22">Mansoor, Farukh</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kanwal%2C+Shamsa%22">Kanwal, Shamsa</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rasheed%2C+Majeeda%22">Rasheed, Majeeda</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kehfulvara%2C+Hafiza%22">Kehfulvara, Hafiza</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ali%2C+Habib%22">Ali, Habib</searchLink><relatesTo>1,7,8</relatesTo> (AUTHOR)<i> habib_ali1417@yahoo.com</i><br /><searchLink fieldCode="AR" term="%22Ullah%2C+Sami%22">Ullah, Sami</searchLink><relatesTo>9</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Al-Sehemi%2C+Abdullah+G%2E%22">Al-Sehemi, Abdullah G.</searchLink><relatesTo>9</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Khan%2C+Muhammad+Sarwar%22">Khan, Muhammad Sarwar</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Joyia%2C+Faiz+Ahmad%22">Joyia, Faiz Ahmad</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> faizahmad1980@gmail.com</i>
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  Data: <searchLink fieldCode="JN" term="%22Process+Biochemistry%22">Process Biochemistry</searchLink>. Nov2021, Vol. 110, p292-301. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Recombinant+proteins%22">Recombinant proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Plasminogen%22">Plasminogen</searchLink><br /><searchLink fieldCode="DE" term="%22Mutant+proteins%22">Mutant proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Glutamic+acid%22">Glutamic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Plasminogen+activators%22">Plasminogen activators</searchLink><br /><searchLink fieldCode="DE" term="%22Serine+proteinases%22">Serine proteinases</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: [Display omitted] • Lumbrokinases are group of serine proteases. • Serine found at position 214 in lumbrokinase improved the activity of lumbrokinase. • In silico tools were used for characterization of mutant Lk-6 proteins. • Serine-Valin214 substitution were direct activation of breaking Arg561-Val562 bond. • The results of this study are step forward towards engineering smart lumbrokinases. Lumbrokinases (LKs) belong to the group serine proteases capable to prevent thrombosis through the proteolysis of both plasminogen-bound and plasminogen-free fibrin molecules. The article presents improved activity of Lumbrokinase-6 (Lk-6) by suggesting the substitution of a Serine found at position 214 (Lk-6) with three other amino acids namely Glutamic acid, Proline and Valine. To characterize the stability, enzyme-substrate interaction and improved activity of three mutant Lk-6 proteins (Lk-Glu214, Lk-Pro214, Lk-Val214) In Silico tools were utilized. Subsequently, Lk-6 wild type and three mutant proteins were subjected to structure prediction, molecular modeling, phylogeny, molecular docking and Protein-Protein Interaction (PPI) using the In Silico tools. Collection and analysis of results revealed that substituted mutation at Ser214 with Valine214 can appreciably stabilize the overall structure of Lk-6 protein and makes its interaction with plasminogen activator physically powerful for higher plasmin activation. Similarly, Serine214 to Valine214 substitution resulted the direct activation of plasmin breakage at the Arg561-Val562 bond. The Arg-Val at position 561–562 in plasminogen and its connection at catalytic site have significantly shown that the predicted residue Valine214 could be further examined through genetic engineering of Lk-6 protein. Therefore, such results are potential steps towards the engineering of smart and active Lks. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Process Biochemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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:
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    Identifiers:
      – Type: doi
        Value: 10.1016/j.procbio.2021.08.022
    Languages:
      – Code: eng
        Text: English
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      Pagination:
        PageCount: 10
        StartPage: 292
    Subjects:
      – SubjectFull: Recombinant proteins
        Type: general
      – SubjectFull: Plasminogen
        Type: general
      – SubjectFull: Mutant proteins
        Type: general
      – SubjectFull: Glutamic acid
        Type: general
      – SubjectFull: Plasminogen activators
        Type: general
      – SubjectFull: Serine proteinases
        Type: general
    Titles:
      – TitleFull: In silico analyses of predicted substitutions in fibrinolytic protein 'Lumbrokinase-6' suggest enhanced activity.
        Type: main
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              M: 11
              Text: Nov2021
              Type: published
              Y: 2021
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