Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands
In silico approaches were employed to examine the characteristics of interactions between human mitochondrial thioredoxin 2 (HsTrx2) and its 38 previously identified mitochondrial protein ligands. All interactions appeared driven mainly by electrostatic forces. The statistically significant residues...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/13/1/15 |
| _version_ | 1827372839288700928 |
|---|---|
| author | Charalampos Ntallis Haralampos Tzoupis Theodore Tselios Christos T. Chasapis Alexios Vlamis-Gardikas |
| author_facet | Charalampos Ntallis Haralampos Tzoupis Theodore Tselios Christos T. Chasapis Alexios Vlamis-Gardikas |
| author_sort | Charalampos Ntallis |
| collection | DOAJ |
| description | In silico approaches were employed to examine the characteristics of interactions between human mitochondrial thioredoxin 2 (HsTrx2) and its 38 previously identified mitochondrial protein ligands. All interactions appeared driven mainly by electrostatic forces. The statistically significant residues of HsTrx2 for interactions were characterized as “contact hot spots”. Since these were identical/adjacent to putative thermodynamic hot spots, an energy network approach identified their neighbors to highlight possible contact interfaces. Three distinct areas for binding emerged: (i) one around the active site for covalent interactions, (ii) another antipodal to the active site for strong non-covalent interactions, and (iii) a third area involved in both kinds of interactions. The contact interfaces of HsTrx2 were projected as respective interfaces for <i>Escherichia coli</i> Trx1 (EcoTrx1), 2, and HsTrx1. Comparison of the interfaces and contact hot spots of HsTrx2 to the contact residues of EcoTx1 and HsTrx1 from existing crystal complexes with protein ligands supported the hypothesis, except for a part of the cleft/groove adjacent to Trp<sup>30</sup> preceding the active site. The outcomes of this study raise the possibility for the rational design of selective inhibitors for the interactions of HsTrx2 with specific protein ligands without affecting the entirety of the functions of the Trx system. |
| first_indexed | 2024-03-08T11:07:30Z |
| format | Article |
| id | doaj.art-a8c49bf8753a4291b15783124ac280a4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T11:07:30Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-a8c49bf8753a4291b15783124ac280a42024-01-26T14:39:35ZengMDPI AGAntioxidants2076-39212023-12-011311510.3390/antiox13010015Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein LigandsCharalampos Ntallis0Haralampos Tzoupis1Theodore Tselios2Christos T. Chasapis3Alexios Vlamis-Gardikas4Department of Chemistry, University of Patras, 26504 Rion, GreeceDepartment of Chemistry, University of Patras, 26504 Rion, GreeceDepartment of Chemistry, University of Patras, 26504 Rion, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, Vas. Constantinou 48, 11635 Athens, GreeceDepartment of Chemistry, University of Patras, 26504 Rion, GreeceIn silico approaches were employed to examine the characteristics of interactions between human mitochondrial thioredoxin 2 (HsTrx2) and its 38 previously identified mitochondrial protein ligands. All interactions appeared driven mainly by electrostatic forces. The statistically significant residues of HsTrx2 for interactions were characterized as “contact hot spots”. Since these were identical/adjacent to putative thermodynamic hot spots, an energy network approach identified their neighbors to highlight possible contact interfaces. Three distinct areas for binding emerged: (i) one around the active site for covalent interactions, (ii) another antipodal to the active site for strong non-covalent interactions, and (iii) a third area involved in both kinds of interactions. The contact interfaces of HsTrx2 were projected as respective interfaces for <i>Escherichia coli</i> Trx1 (EcoTrx1), 2, and HsTrx1. Comparison of the interfaces and contact hot spots of HsTrx2 to the contact residues of EcoTx1 and HsTrx1 from existing crystal complexes with protein ligands supported the hypothesis, except for a part of the cleft/groove adjacent to Trp<sup>30</sup> preceding the active site. The outcomes of this study raise the possibility for the rational design of selective inhibitors for the interactions of HsTrx2 with specific protein ligands without affecting the entirety of the functions of the Trx system.https://www.mdpi.com/2076-3921/13/1/15thioredoxinmitochondriahot spotscontact areainterfacemolecular recognition |
| spellingShingle | Charalampos Ntallis Haralampos Tzoupis Theodore Tselios Christos T. Chasapis Alexios Vlamis-Gardikas Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands Antioxidants thioredoxin mitochondria hot spots contact area interface molecular recognition |
| title | Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands |
| title_full | Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands |
| title_fullStr | Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands |
| title_full_unstemmed | Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands |
| title_short | Distinct or Overlapping Areas of Mitochondrial Thioredoxin 2 May Be Used for Its Covalent and Strong Non-Covalent Interactions with Protein Ligands |
| title_sort | distinct or overlapping areas of mitochondrial thioredoxin 2 may be used for its covalent and strong non covalent interactions with protein ligands |
| topic | thioredoxin mitochondria hot spots contact area interface molecular recognition |
| url | https://www.mdpi.com/2076-3921/13/1/15 |
| work_keys_str_mv | AT charalamposntallis distinctoroverlappingareasofmitochondrialthioredoxin2maybeusedforitscovalentandstrongnoncovalentinteractionswithproteinligands AT haralampostzoupis distinctoroverlappingareasofmitochondrialthioredoxin2maybeusedforitscovalentandstrongnoncovalentinteractionswithproteinligands AT theodoretselios distinctoroverlappingareasofmitochondrialthioredoxin2maybeusedforitscovalentandstrongnoncovalentinteractionswithproteinligands AT christostchasapis distinctoroverlappingareasofmitochondrialthioredoxin2maybeusedforitscovalentandstrongnoncovalentinteractionswithproteinligands AT alexiosvlamisgardikas distinctoroverlappingareasofmitochondrialthioredoxin2maybeusedforitscovalentandstrongnoncovalentinteractionswithproteinligands |